Cottonseed meal is widely used as an alternative source of protein in the animal feed industry. However, the presence of toxic gossypol limits its use in livestock production. In order to reduce gossypol toxicity, microbial degradation is generally considered to be an environmentally friendly and cost-effective strategy. Candida tropicalis ZD-3 has demonstrated the ability to degrade gossypol. Nevertheless, the genome of gossypol-induced C. tropicalis ZD-3 has not been fully sequenced, and its comprehensive metabolic profile remains unexplored. In this study, the degradation rate of gossypol by ZD-3 reached 88.5 %, as determined by high performance liquid chromatography (HPLC). The characteristic peaks of amides were changed after gossypol treatment by Fourier transform infrared spectroscopy (FTIR) analysis. Genomic correlation results showed that gene function annotation revealed 64 protein-coding genes potentially involved in gossypol catabolism, primarily encoding aldehyde dehydrogenase, aldehyde reductase, and glutathione peroxidase. Metabolomic analysis indicated that gossypol activated ABC transporters and amino acid synthesis pathways, such as histidine, lysine, and arginine biosynthesis. These pathways provided substantial energy for C. tropicalis ZD-3 cells to cope with external stress, promoted the tricarboxylic acid (TCA) cycle, and formed a complex regulatory network for gossypol tolerance and degradation. This study marks the first revelation of gossypol metabolism in C. tropicalis, laying a foundation for further research on gossypol degradation and detoxification.