The aim of this study was to assess the effect of empagliflozin and/or calcipotriol on cadmium-induced testicular toxicity in rats. Sixty male Wistar rats were divided into 6 equal groups: Control; cadmium; cadmium + empagliflozin; cadmium + calcipotriol; cadmium + Carboxymethyl cellulose and cadmium + empagliflozin + calcipotriol. Testicular enzymes, serum testosterone, luteinizing hormone and follicle stimulating hormone were measured. Also, testicular tissue antioxidant enzymes, interleukin-6 (IL-6), transforming growth factor beta 1 (TGF-β1) and sperm characteristics were determined. Parts of the testes were subjected to histopathological and immunohistochemical examination. Empagliflozin/calcipotriol combination restored the testicular enzymes, sperm characteristics, hormonal profile and the antioxidant defenses compared to the use of each of these drugs alone. Also, this combination significantly ameliorated the inflammatory processes and induced significant improvement of the histopathological, and immunohistochemical picture compared to the use of each of these drugs alone. So, empagliflozin/calcipotriol combination might represent a promising therapeutic modality for amelioration of cadmium-induced testicular toxicity.