In vivo toxicity and antifungal therapeutic evaluation of selected natural compounds for topical applications was analyzed using standard methods. The natural compounds, blue vitriol, brimstone, trona, alum, palm ash and black stone were hygienically selected and purchased at a local market in southeastern Nigeria. The test organisms were isolated from high vaginal swab specimens obtained from cases of cutaneous candidiasis. The isolates were identified based on their morphological, physiological and molecular characteristics. The toxicological screening of the test samples was done using Draize’ skin irritancy test, Murine local lymph node assay (LLNA) and necropsy. The in vivo evaluation of antifungal activity of the solutions was done using eight-week-old albino rats weighing 120g – 150g. The animals were infected with the Candida isolates percutaneously; and treated using various formulations of the natural compounds. The skin sections were carefully observed for histopathological changes, before and after treatment. The total yeast counts of the infected skin tissues were also determined. The isolates include Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis. Draize’ skin test and Murine local lymph node assay showed no observable skin irritancy reaction (P>0.05). The normal skin architecture of the infected animals was restored after 5 days of treatment with the test samples; while the total yeast count decreased from 108 CFU/mL to 102 CFU/mL. The findings have revealed that natural compounds are effective as well as non-toxic topically, in treatment of cutaneous candidiasis.