Objective To investigate the effect and mechanism of Zuogui pill-containing serum (ZGP-containing serum) on chemotherapy-damaged granular cells (GCs) and theca cells (TCs).Methods GCs and TCs were cultured respectively, the model group was established with phosphoramide mustard (PM), then treated by ZGP-containing serum. The survival rates of GCs and TCs was determined by CCK-8. Real-time fluorescent quantitative PCR (RT-PCR) and Western blot methods were used to detect the expression of Beclin-1, light chain 3 (LC3B), p62, Bax and Caspase3.Results 10% ZGP-containing serum had the best effect on the recovery of cell survival rate. Compared with the blank control group, Beclin-1, LC3B, Bax and Caspase3 have higher expression in the model group (P<0.05), and 10% ZGP-containing serum can down-regulate the expression of them (P<0.05). Moreover, the expression of p62 is lower in the model group than the blank control group (P<0.05), and 10% ZGP-containing serum can up-regulate it (P<0.05). In addition, in the groups of GCs, after activating or inhibiting the autophagy pathway, the expression of autophagy-related proteins and apoptosis-related proteins both changed correspondingly.Conclusion PM can damage GCs and TCs by promoting apoptosis and activating autophagy/lysosomal degradation pathways, 10% ZGP-containing serum can alleviate the damage. There is a cross-talk between autophagy and apoptosis in the process of PM damaging GCs which can be alleviated by 10% ZGP containing serum.