This study focuses on the development and evaluation of a nanosuspension containing ethanolic extracts of Tinospora cordifolia and Syzygium cumini for managing Diabetes mellitus. The main objective is to create an effective polyherbal nanosuspension by combining Tinospora cordifolia and Syzygium cumini with an optimal concentration of chitosan polymer to address Diabetes mellitus. Furthermore, both in vitro and in vivo assessments of the synthesized nanosuspensions were conducted to determine the best formulation. Methods and Findings: The ethanolic extracts of the mentioned plants were obtained using a maceration technique, followed by preliminary phytochemical screening, HPTLC analysis, and FTIR-based incompatibility assessments. The nanosuspension was prepared using the ionic gelation method by varying the chitosan polymer concentration. Comprehensive in vitro assessments were carried out, including measurements of pH, viscosity, drug content, entrapment efficiency, loading capacity, and in vitro release profiles for different formulations. The formulation with the highest drug content and optimal release characteristics was selected for further analysis of particle size, zeta potential, and surface morphology. Subsequently, the antidiabetic efficacy of the polyherbal nanosuspension was evaluated using wistar albino rats. Discussion: FTIR analysis indicated no significant interaction between the drug and the polymer. The in vitro drug release and kinetic analyses suggested that the F5 formulation exhibited superior drug release and an improved release mechanism. The particle size was determined to be approximately 420nm, and SEM imaging revealed particles that were nearly spherical in shape. Stability assessments of formulation F5 demonstrated consistent physical and chemical parameters over time.