Background GlucoMedix® is an all-natural phytotherapy consisting of a hydro-alcoholic extract of Stevia rebaudiana (Bertoni) Bertoni and pentacyclic chemotype Uncaria tomentosa (Willd. Ex Schult.) DC. The nutraceutical product has potential for the treatment of hyperglycemia in type 2 diabetes and Metabolic Syndrome. Methods Six adult Hispanic type 2 diabetic patients were included in an outpatient retrospective open label physician-sponsored case series study. GlucoMedix® extract of Stevia plus pentacyclic chemotype Uncaria was administered orally at doses of 2 ml, diluted in water, two or three times daily. The patients’ blood glucose levels were recorded historically, at baseline, and thereafter while taking GlucoMedix® orally. Results When treated with GlucoMedix®, with or without coincident advice to modify diet, all six patients manifested reductions in blood glucose levels. At baseline four of the six patients were administering one or more prescription treatments for hyperglycemia, e.g., Glibenclamide, Metformin, Vildagliptin, or Insulin. Two patients displayed substantial reductions in glucose of 50 and 70 mg/dl, and in conjunction with the removal of their prior drug treatments of Glibenclamide plus Metformin or of Vildagliptin. An Insulin-treated patient experienced a 50 mg/dl reduction while ceasing Metformin and was subsequently able to reduce the dose of Insulin by half. Thus, in three patients GlucoMedix® abrogated in whole or in part the requirement for pharmaceutical or biologic therapies to achieve substantial beneficial reductions in glycemic levels. Conclusions In this proof-of-principle study oral GlucoMedix® was an effective treatment for hyperglycemia in type 2 diabetic individuals. This all-natural phytotherapy can be used beneficially in conjunction with existing pharmaceutical or biological therapy regimens, and in some cases can replace in whole or in part the requirement for pharmaceutical or biologic therapies. These in-life results suggest that this natural product approach can serve as an alternative to prescription monotherapies or multimodal therapies for the regulation of hyperglycemia.