The present study aimed to investigate the Phytochemical invstigation, Docking, Anti-inflammatory activity from the seed extracts of Erythrina variegata by using Zebra fish model and Insilico method. Phytochemical analysis confirmed the presence of alkaloids, flavonoids, tannins, triterpenoids, saponins, and glycosides. GC–MS revealed stigmasterol, β-sitosterol, and prenylated flavonoids as major constituents. Acute toxicity studies established safety up to 100 mg/L (LD50 > 100 mg/L). Ethanolic extract (100 mg/L) inhibited carrageenan - induced edema by 48.6%, while chloroform extract reduced edema by 42.3%, compared with Indomethacin (10mg/kg). Histopathology showed only mild to moderate changes in extract-treated groups versus severe alterations in carrageenan controls. Docking studies revealed strong binding of stigmasterol and β-sitosterol with COX1 and COX-2. ADME analysis indicated high GI absorption, favourable log P values (3.5–4.2), TPSA < 100, and compliance with Lipinski’s Rule. Protox3.0 categorized the major phytoconstituents under Toxicity Class 5 (LD50 ≈ 2000 mg/kg) with no hepatotoxic, mutagenic, or carcinogenic alerts. Erythrina variegata seed extracts demonstrated significant anti-inflammatory activity in zebra fish and exhibited favourable pharmacokinetic and safety profiles in Insilico method. These findings provide scientific validation for its traditional use and highlight its potential as a natural source of safe and effective Anti-inflammatory agents.