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Type-2 diabetes mellitus remains a major global health challenge, requiring therapeutic strategies that ensure long-term safety while addressing its multifactorial pathology. Although existing pharmacotherapies effectively control glycemia, their largely single target mechanisms and variable tolerability underscore the need for complementary approaches. In this study, we present a comprehensive evaluation of NAMIG-5, an polyherbal formulation, for Type-2 diabetes mellitus management. Pharmacognostic and phytochemical analyses using spectroscopic and chromatographic techniques, confirmed the authenticity of the formulation along with the chemical consistency. In a nicotinamide-streptozotocin-induced diabetic model, NAMIG-5 exhibited significant antihyperglycemic activity without acute or sub-chronic toxicity. A randomized, active-controlled clinical trial involving 90 participants demonstrated significant reductions in fasting and postprandial glucose levels, improved lipid profiles, and excellent tolerability, with efficacy exceeding metformin, a widely prescribed anti-diabetic medication (p < 0.05). Mechanistically, the components of NAMIG-5 synergistically inhibited human islet amyloid polypeptide aggregation. Bioactivity-guided fractionation identified the key active constituents, establishing NAMIG-5 as a safe therapeutic candidate for Type-2 diabetes mellitus.