Pericopsis laxiflora (Benth) Meeuwen is used in African folk medicine to mitigate numerous infections. This study evaluated the antioxidant, phytochemical and antimicrobial activities and protective potential of P. laxiflora methanol leaf extract against cadmium-induced testicotoxicity in male Sprague–Dawley rats. The methanol extract of P. laxiflora leaves (MLPL) obtained by cold maceration contained several phytochemicals, but no cardiac glycosides or terpenoids were found. It showed remarkable dose-dependent in vitro antioxidative activity. The extract had similar antibacterial effects as ciprofloxacin against Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. However, it was more effective against S. pneumoniae than the other bacterial strains. Similarly, it exhibited antifungal activities comparable to Griseofulvin against Candida albicans and Aspergillus spp. The extract corrected the damage occasioned by intoxication with CdCl2. It elevated testicular malonaldehyde like Quercetin. The increased NO and myeloperoxidase (MPO) activities induced by treating Sprague–Dawley rats with CdCl2 were significantly reduced by the MLPL extract. The extract also attenuated the production of β-catenin and B-cell lymphoma 2 (BCL-2) protein in the testiculocytes of the rats and restored severe perivascular inflammation in liver cells. Through several mechanisms, MLPL showed protective effects against testis injury induced by cadmium chloride in Sprague–Dawley rats.