Azadirachta indica A. Juss (neem) is a popular plant in Vietnam that possesses strong hypoglycemic effects. However, limited research reports the formulation of the neem extract in a pharmaceutical dosage form. Thus, this work determined the development and in-vitro/in-vivo evaluation of the film-coated tablets containing neem leaf extract, with moisture-protected ability, for diabetes treatment. To this end, we first investigated the neem leaf’s optimal extraction conditions to obtain the extract with the strongest hypoglycemic effect. The best condition was the utilization of ethanol 90% as a solvent, with a plant solid-to-solvent ratio of 1:10 w/w. Then, the optimal film-coated tablet formulations were determined by varying the types/amounts of the tablet adsorbents, diluents, binders, disintegrants, and moisture-resistant film-coating polymers. The best formulation possessed good moisture resistance compared to commercial products and acceptable friability and disintegration values. Finally, the product was evaluated for its antidiabetic property by both in-vitro and in-vivo tests, utilizing the α-glucosidase inhibitory assay and mice glucose tolerance test, respectively. The tablets showed significant hypoglycemic effects in inhibiting the α-glucosidase enzyme (43.33% compared to 55.16% of the commercial drug Glucobay) and in-vivo test in mice. In summary, the film-coated tablets containing A. indica A. Juss leaf extract had potential antidiabetic effects in in-vitro/in-vivo settings.