Research was carried out for the appraisal of toxic and anti-enzymetic action of acetone extracts of Datura inoxia and Azadirachta indica against Tribolium castaneum, Trogoderma granarium and Sitophilus granarius in the grain research training and storage management cell of department of entomology and in protein molecular biology laboratory (PMBL) department of biochemistry (UAF) during the year 2014. Various dilution levels viz., 5.0, 10.0, 15.0 and 20.0% of both plants extracts were assessed against test insects. Toxic effect of plant extracts in T. castaneum, T. granarium and S. granarius was observed after an exposure period of 2, 4, 6, 8 and 10 days while inhibition of different enzymes acetylcholinesterase (AChE), a-carboxylesterase (alpha-CE), beta-carboxylesterase (beta-CE), acid phosphatases (ACP) and alkaline phosphatases (ALP) were calculated spectrophotometrically in the survivors of toxicity assay. The results evidenced that both plant extracts had lethal effects against three stored grain insect species. Comparison of means of mortality in T. castaneum, T. granarium and S. granarius proved that A. indica extract was more effective, causing maximum 38.41, 24.35 and 28.56% mortality, respectively. D. inoxia resulted in 15.12, 13.52 and 14.07% maximum mortality in T. castaneum, T. granarium and S. granarius, respectively. The results also revealed significant inhibition of AChE, alpha-CE, beta-CE, ACP and ALP upon exposure to various concentrations of tested plants. Plant extract of A. indica proved more efficient for the inhibition of all test enzymes in three stored grain insect pests. The results suggest the ability of using these plants extracts for wheat flour and grains protection as a safe alternative to insecticides.