Objective This study aims to evaluate the therapeutic effects of Zhenwu Decoction (ZWD) on a cisplatin toxicity model and an H22 tumor-bearing model in mice, while elucidating its mechanism of action through metabolomics, thereby providing a foundation for clinical application. Methods A cisplatin toxicity model was established in mice, utilizing body weight, the tail suspension test, 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. Concurrently, liquid chromatography-mass spectrometry (LC-MS) combined with multivariate statistical analysis was employed to screen and identify differential metabolites based on the human metabolic database (HMDB). Results The extract of Zhenwu Decoction significantly mitigated weight loss (P<0.0001), depressive-like behavior, reduced organ weight (P<0.05), and abnormal platelet count (P<0.05) in mice subjected to cisplatin-induced toxicity. Additionally, it exhibited a notable trend toward tumor suppression in H22 tumor-bearing mice. Serum metabolomics analysis indicated that, in the cisplatin group, two differential metabolites were downregulated following treatment with the extract of Zhenwu Decoction, while five metabolites were downregulated after treatment with the alcohol extract. Conclusion The extract of Zhenwu Decoction significantly alleviates cisplatin toxicity in mice and demonstrates a trend toward tumor suppression. 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.