The Mascarene Aloes are used in the traditional pharmacopoeia against various ailments including cutaneous diseases and as antispasmodics. Scientific evidence to support these claims is non-existent and mainly based on the scientific repute of A. vera. The antioxidant profile of methanolic leaf extracts of A. purpurea Lam., A. tormentorii (Marais) L. E. Newton & G. D. Rowley, A. lomatophylloides Balf. f., A. macra Haw. and A. vera (L.) Burm. f. was studied using the total antioxidant capacity, copper equivalent and superoxide dismutase assays. In vitro cytotoxicity was evaluated on CAD (Cath.-a-differentiated) neuronal cells by the methyl tetrazolium assay, and the neuroprotective profile was assessed using hydrogen peroxide-induced neurotoxicity with the CAD cells. The aloin and vitexin content were determined by high-performance liquid chromatography with diode-array detection. A. purpurea had the highest aloin content (546.6 nmol/g), while A. tormentorii had the highest vitexin content (67.3 nmol/g). A. macra (concentration <0.1 mg/mL) elicited a 10% cytotoxicity effect on CAD cells while other Mascarene Aloes were not cytotoxic. This study validates the antioxidant and neuroprotective potential of Mascarene Aloes focusing on their aloin and vitexin content that are also present in other reputed medicinal Aloes.