Background: The effects of D-ribose L-cysteine on nicotine-induced testicular toxicity in male Wistar rats were examined in this study. Twenty healthy adult male Wistar rats with an average weight of 200 g were grouped as normal control, nicotine (2 mg/kg), D-ribose L-cysteine (30 mg/kg) + nicotine (2 mg/kg), and D-ribose L-cysteine (30 mg/kg). The animals were administered intraperitoneally for 35 days consecutively. Epididymal sperm concentration, motile count, total counts, morphology, and progressive assessment were estimated. Antioxidant levels, tissue protein and testicular histology were also assessed. Results: This study showed reduced antioxidant levels (catalase, super-dioxide dismutase, and glutathione peroxidase) and increased malondialdehyde levels in the nicotine group relative to normal control group, D-ribose L-cysteine group and D-ribose L-cysteine + nicotine group. This study also showed significant reduction in testicular mass, sperm motile count, concentration, total count, and morphology in nicotine group (p < 0.05) compared to normal control group and D-ribose L-cysteine groups. There was improvement in sperm motility, viability, morphology, counts, in group co-treated with D-ribose L-cysteine, and nicotine relative to nicotine group. Likewise, the degenerative seminiferous tubule histoarchitecture due to nicotine was improved by D-ribose L-cysteine. Notably, the D-ribose L-cysteine group showed superlative values in all investigated parameters relative to the other groups. Conclusion: This study demonstrated the ability of D-ribose L-cysteine to mitigate the toxic effects of nicotine on reproductive functions in male Wistar rats. It also demonstrated the pro-spermatogenic properties of the compound in boosting andrological parameters.