Cyclophosphamide (CPAm) is a widely used chemotherapeutic agent that exhibits potent anti-cancer properties but is often associated with debilitating side effects. Despite its efficacy, the management of CPAm-induced toxicities remains a significant clinical challenge. There has been growing interest in exploring complementary and alternative therapies to mitigate these adverse effects in recent years, and this may be a chance for the earthworm-derived preparation, Venetin 1. Its rich composition of bioactive compounds has demonstrated promising pharmacological properties, including anti-inflammatory, antioxidant, and immunomodulatory effects. These properties suggest its potential to counteract the various systemic toxicities induced by CP. To investigate the effect of Venetin 1 on cyclophosphamide-induced toxicity, we conducted a comprehensive study. Mice were administered CPAm for four days, followed by the earthworm preparation in two doses (50 mg/kg and 100 mg/kg b.w). Importantly, the preparation did not cause any side effects in all mice, ensuring the safety of the intervention. We then determined global changes in the proteome using proteomics and quantitative SWATH-MS analysis, a robust and reliable method. This allowed us to identify up- and downregulated proteins in each studied group, providing valuable insights into the mechanism of action of Venetin 1. According to the obtained results, Venetin 1 significantly affected the proteome of mouse lung tissue. It was possible to determine quantitative changes for 400 proteins, and the analysis after administration of Venetin 1 showed a change in the global proteomic profile from upregulated to down-regulated. The stimulating properties of the preparation concerning the complement system have also been confirmed in a separate validation experiment. It has been shown that Venetin 1 has the potential to eliminate the toxic effect of cyclophosphamide in lung tissue. It also initiates regenerative processes, inhibits inflammatory processes, supports autophagy and stimulates the immune system. Further research is required to understand and to fully describe the effects of Venetin 1 .