Objective This study aimed to evaluate the therapeutic effects of Zhenwu Decoction on a cisplatin toxicity model and an H22 tumor-bearing mouse model, elucidating its mechanism of action through metabolomics to provide a foundation for its clinical application. Methods A cisplatin toxicity model was established in mice, utilizing body weight, tail suspension testing, organ weights, and platelet counts as indices for efficacy evaluation. Additionally, an H22 tumor-bearing mouse model was created, with tumor weight serving as the efficacy index. Liquid chromatography-mass spectrometry combined with multivariate statistical analysis was employed to screen and identify differential metabolites based on the human metabolic database. Results The extract of Zhenwu Decoction significantly mitigated weight loss ( P<0. 000 1), depressive-like behavior, reduced organ weight ( P<0. 05), and abnormal platelet counts (P<0. 05) in mice subjected to cisplatin-induced toxicity. Additionally, it had a certain inhibitory trend on tumor growth in H22 tumor-bearing mice. Serum metabolomics indicated that two differential metabolites were downregulated following extract of Zhenwu Decoction treatment in the cisplatin group,while five metabolites were downregulated after treatment with the alcohol extract. Conclusions The extract of Zhenwu Decoction alleviated cisplatin toxicity in mice and showed a certain inhibitory trend on the growth of mouse tumors. Its efficacy may be associated with the modulation of substances such as 7-HDoHE, (E)-8-(4-hydroxy-6- methoxy-7-methyl-3-oxo-1h-2-benzofuran-5-yl )-2, 6-dimethyloctano-6-enoic acid and N-acetyl-carnosine. These findings provide a theoretical basis for further research into the clinical application of Zhenwu Decoction and its combination with cisplatin in cancer treatment.