Multiple experiments using diabetes animal models have demonstrated the antihyperglycemic properties of several Mexican Copalchi species, mainly Hintonia latiflora (HLA) and Hintonia standleyana (HSL). The active compounds of these plants have recently been characterized and their therapeutic mechanisms proposed. Though widely studied in animals, evidence indicating therapeutic efficacy in patients with non-insulin-dependent diabetes mellitus (NIDDM) is limited. Still, copalchis have been utilized as a folk remedy, and in Germany as a marketed drug, for managing NIDDM. The risks and benefits of using this drug warrant critical analysis. This review summarizes research evidence for the antidiabetic efficacy of Copalchis in NIDDM animal models, recent toxicity findings, and limited clinical findings in human subjects.