The current study investigated the protective ameliorative effect of intraperitoneally administered kisspeptin-10 (50 nmol/day) against reproductive toxicity in adult male mice challenged with 35 days of exposure to sodium arsenite in drinking water. Mice were divided into tap water control, sodium arsenite-alone (4 ppm and 10 ppm), kisspeptin-alone (intermittent and continuous) and combined (sodium arsenite +kisspeptin-10 intermittent and continuous) treatment groups. Results revealed protective effect of both intermittent and continuous kisspeptin doses on reproductive organs against sodium arsenite-induced toxicity. This was indicated by an increase (p < 0.001) in the activity of antioxidant enzymes and a decrease (p < 0.001) in the levels of oxidative stress biomarkers. Concomitant significant increase was noticeable in the relative organ weight (p < 0.01), and serum testosterone and seminal fructose (p < 0.001), and a significant improvement in sperm parameters was also observed. A significant downregulation of lactate dehydrogenase concentration demonstrated further the protective effect of kisspeptin against tissue damage. Histologically, both treatment regimens of kisspeptin combined with sodium arsenite exposure prevented massive germ cell loss and tissue damage, a condition prominent in sodium arsenite-alone-treated mice. The study demonstrates for the first time kisspeptin's potential to mitigate the biochemical and histotoxic effects of arsenic on male reproductive system.