Objective Clinical evidence and cellular models have shown an inverse relationship between the intakes of plant and fruit based diets and oxidative stress, suggesting the suitability of natural antioxidants in the management of diabetes mellitus and its complications. Method A randomized controlled clinical trial was conducted at the Cardiac Centre, SSRN Hospital, Pamplemousses, (Mauritius) to determine the effect of a short term supplementation of a fermented papaya preparation (FPP®) on biomarkers of diabetes and antioxidant status in a multi-ethnical neo-diabetic population from November 2010 to March 2011. Result Supplementation of 6 g FPP®/day for a period of 14 weeks could improve the general health status of several organs targeted by oxidative stress during diabetes. When comparing experimental to control groups with independent samples t-test, C-reactive protein levels significantly decreased (P = 0.018), LDL/HDL ratio was considerably changed (P = 0.042), and uric acid levels were significantly improved (P = 0.001). ANOVA results also validated the same findings with significant differences in C-reactive protein, LDL/HDL ratio, uric acid and in serum ferritin levels. Conclusion FPP® may present a novel, economically feasible nutraceutical supplement for the management of diabetes and for those at risk for cardiovascular disease, neurological disease and other conditions worsened by overt inflammation and oxidative stress.