Spores and pollen, as ubiquitous organisms found in nature, possess a remarkable core-shell structure and intricate surface morphology. These tiny particles are notable for their dimensional uniformity, sustainable utilization, environmental friendliness, porosity, amphiphilicity, and strong adhesive properties. In addition, they display excellent biocompatibility and biodegradability, which significantly enhances the stability and targeting of drugs within the body. Spores and pollen can be extracted using methods such as acidic solutions, alkaline solutions, or enzyme treatments to obtain sporopollenin, which is an extremely resilient and chemically inert complex biopolymer. The sporopollenin extracted through this process removes the original bioactive substances, such as cell nuclei, enzymes, and DNA, providing greater drug loading capacity and containing no potential allergens or immunogens, thus further enhancing its drug loading capacity and improving safety in therapeutic applications. Due to these beneficial attributes, spores, pollen and sporopollenin have gained widespread use in a variety of drug delivery systems, such as targeted delivery, sustained drug delivery, toxicity mitigation, flavor masking, vaccine delivery, delivery of labile substances, and other applications. This review introduces the types of natural spores and pollen commonly used in drug delivery systems, including their main components, common effects, and uses in drug delivery systems, and so on. It subsequently summarizes novel optimization methods in their processing, such as physical treatment, surface modification, and chemical modification, which enable higher drug loading efficiency, stability, and targeting, among other benefits. Additionally, this paper reviews the research progress and applications of natural spores, pollen, and sporopollenin in drug delivery systems, while also touching on some innovative research content, such as novel nanomotor microcarriers developed based on pollen. Based on these research findings, we further elaborate on the advantages of spores, pollen, and sporopollenin in drug delivery systems. For example, they have high stability and drug loading capacity, good adhesion, excellent targeting, and are easy to modify functionally. Currently, they show promising prospects in the fields of targeted drug delivery, sustained-release drug delivery, as well as the delivery of drugs that are effective but slightly toxic, and are often used in research on the treatment of diseases such as cancer and inflammation. We have also highlighted the challenges they face in various applications and identified some issues that need to be addressed, including difficulties in large-scale production, the need to improve extraction and purification processes, and the existence of a low but still noteworthy risk of allergies, in order to fully leverage their potential in drug delivery applications. According to current research, although spores, pollen, and sporopollenin face some unresolved issues in clinical drug delivery, they still have great potential overall and are expected to become a new generation of green drug delivery platforms. In the future, further research into their unique physical and chemical properties and structural characteristics will help develop more efficient and stable drug delivery systems to meet diverse treatment needs. We believe that continued exploration of natural spores, pollen, and sporopollenin will drive this emerging field to achieve continuous breakthroughs and progress, ultimately making an important contribution to the cause of human health.