Platelets play a crucial role in hemostasis and thrombosis. They have a complex and active metabolic system, particularly regarding lipid metabolism. The active and intricate lipid metabolism within platelets plays a central role in platelet activation, signal transduction, and functional regulation, making it crucial for studying the pathophysiological mechanisms of diseases. The platelet membrane structure is highly complex and it contains various lipids, including phospholipids, sphingolipids, cholesteryl esters, and triglycerides, etc. Current research has elucidated multiple metabolic pathways in platelets, such as phospholipid and sphingolipid metabolism, which profoundly influence platelet aggregation, release, and inflammatory responses. Upon activation, platelets release various lipids that interact with inflammatory cells in a paracrine manner. This review systematically describes the key lipid metabolism in platelets and its dynamic functional regulation. Lipid metabolism regulates processes such as platelet production, aging, and activation. This review emphasizes the interaction between lipid droplets and mitochondria, which is closely related to platelet activation. For instance, platelet-derived extracellular vesicles can transfer dysfunctional mitochondria from platelets to hepatocytes, leading to the dysfunction of lipid droplet-bound mitochondria and abnormal lipid droplet metabolism, thereby affecting hepatic lipid metabolism. The review summarizes interactions between platelet lipid metabolism and other cells, including leukocytes, erythrocytes, and lymphocytes. However, there are few studies on the interactions between platelets and cells through lipid metabolism, and the direct evidence is scarce. Further research is recommended in the future. It further explores the relationships between platelet lipid metabolism and the reproductive system, musculoskeletal system, the central nervous system, and the gut microbiota. Additionally, it reviews the close associations between platelet lipid metabolism and diseases such as diabetes, metabolic dysfunction-associated steatotic liver disease, immune thrombocytopenia, metabolic syndrome, and thrombotic disorders (thromboembolic diseases). For example, antiphospholipid syndrome (APS), typically characterized by reproductive impairment, may be associated with enhanced platelet activation and elevated phospholipase A2 activity in patients with APS. Moreover, lipid metabolism in the bone marrow microenvironment can promote platelet production. Under cellular stress, platelets transfer mitochondria to macrophages; in the spinal cord injury model, this process can regulate energy and lipid metabolism, leading to nerve and myelin regeneration and ultimately promoting the recovery of motor function. These findings indicate that modulating energy and lipid metabolism can influence platelet function, suggesting that targeting platelet lipid metabolism may provide a direction for disease treatment. Furthermore, the review covers the research on platelet lipid metabolism and related drugs, including traditional Chinese medicines and natural products. As the first selective 12-lipoxygenase (12-LOX) inhibitor to enter clinical trials, ML355 will facilitate future research on the biology of 12-LOX and its effects on regulation of platelet activity, hemostasis, and thrombosis, and promote the discovery of structure-based drugs. However, research on platelets and lipid metabolism still faces numerous challenges. For example, lipid droplet-mitochondria interaction in the liver regulates lipid metabolism. Meanwhile, there is controversy over whether autophagy serves a protective function or promotes the occurrence of liver disease. It is speculated that the interaction between mitochondrial autophagy and lipid droplets may be a future research direction. The precise regulatory mechanism of lipid metabolism and how to develop novel antithrombotic and anti-inflammatory drugs with high specificity and low side effects by targeting lipid metabolism remain current challenges. In summary, this review provides a comprehensive overview of platelet lipid metabolism, its interactions with other cells, and its roles in organ function and diseases. This contributes to the discovery of new disease-specific lipid biomarkers and drug targets. Future research could focus on structural modifications of drugs targeting lipid metabolism to enhance selectivity, offering directions for improving safety and efficacy, and developing the most effective individualized treatment plans for patients.