Pistacia atlantica is a tree that lives in arid and semi-arid places. Its species have been used in traditional medicine since prehistoric times in several countries for treating cancer, diabetes, and inflammation. We endeavored to continue the previous studies on P. atlantica by working on its hand collected pure pollens aqueous extracts (PAPA) for the first time and discover its bioactive compounds and examine their possibility of interactions against oxidation, inflammation and hyperglycemia in-vitro and in-silico. The total phenolic contents and flavonoids were quantified and identified spectrophotometrically and with LC-MS-MS analysis. Antioxidant activity was measured using (DPPH, ABTS free radicals and FRAP). (BSA) denaturation was estimated for the inflammation test. The anti-hyperglycemic was using alpha-amylase enzyme. The results showed a good content of total phenolic compounds in all samples with (84.34 f 0.81 mg GAE/g DM) and flavonoids (22.61 f 0.16 mg QE/g DM) as the highest values. The DPPH, ABTS and FRAP tests proved very remarkable antioxidants (59.80 f 1.53 mg/g), (0.72 f 0.00 mg/g), (4.30 f 0.01 mg/g) and IC50 (0.035 mg/mL), (2.30 mg/mL) and (0.51 mg/mL) respectively. Regarding alpha-amylase inhibition, PAPA exhibited (386.40 f 4.71 mg AcE/g DM), while the denaturation protection of (BSA) represented (33.90 f 1.77 mg DcE/g DM). The LC-MS-MS analysis exhibited 13 phenolic compounds such as Caffeic acid, Epicatechin, Quercetin and Resveratol. The in-silico study revealed that PAPA compounds interacted strongly with the amino acids of the active site and gave a good docking scores. Pollens from Pistacia atlantica resulted favorably with larger phenolic compounds composition and detailed antioxidant, anti-inflammation and also the potential to contain active ingredients for hyperglycemic therapy. For that, these pollens are suggested to be involved in pharmaceutical and therapeutic fields and used as a functional food.