Oxidative stress is a pathological condition that plays crucial roles in the pathogenesis of various diseases. This study evaluated the antioxidant and toxicological effects of verbenone enhanced with cyclodextrin and lysine in diclofenac induced oxidative stress mice. Adult Swiss mice (35) were randomly distributed into seven (7) groups, induced with oxidative stress and orally administered verbenone, lysine, cyclodextrin, verbenone-lysine, and verbenone-cyclodextrin at 200 mg/kg body weight for seven (7) days. Cyclodextrin treatment significantly increased (p<0.05) total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglycerides compared with diclofenac control. No significant alterations (p<0.05) were observed in very low density lipoprotein cholesterol (VLDL), while a significant increase (p<0.05) was observed with diclofenac treatment in liver triglycerides. No significant alterations (p<0.05) were observed with atherogenic index while cyclodextrin significantly increased cardiac index and coronary artery index. Plasma protein and catalase activities decreased significantly (p<0.05) in all treatment groups. No significant alterations (p<0.05) were observed in malondialdehyde and liver superoxide dismutase. Glutathione peroxidase activity decreased in plasma for verbenone, cyclodextrin, and verb-cyclodextrin, but increased in the liver with lysine and cyclodextrin treatments. Liver albumin and total bilirubin were elevated in treatments, while gamma-glutamyl transferase activity significantly increased (p<0.05) across all groups except with verbenone treatment. Histopathology revealed periportal inflammation in verb-lysine, and while liver and kidney architecture in verb-cyclodextrin and verbenone groups was preserved. The study reveals complex interactions between diclofenac-induced oxidative stress and the modulatory effects of verbenone, lysine, and cyclodextrin. Verbenone and the various mitigated oxidative damage, with cyclodextrin conjugation presented more safety profile compared to lysine conjugation. The combination of verbenone and lysine or cyclodextrin may provide valuable insights into the modulation of renal and hepatic functions under oxidative stress conditions.