Traditionally, Nypa fruticans has been widely used as an herbal remedy, inspiring research into new drug development. This research aimed to explore the phytochemicals of the ethanol extract of Nypa. fruticans leaves (ENFL) to identify potential compounds for treating pain and inflammation. Several methods were employed to assess the in-vitro antioxidant activity. The anti-inflammatory effects were calculated utilizing a formalin-induced inflammation model. Additionally, in-vivo analgesic activity was evaluated following an acetic acid-induced writhing test, hot plate test, and tail immersion test. Metabolites of ENFL identified via GC-MS were then subjected to computational analysis against the cyclooxygenase-2 enzyme to explore potential lead compounds. Twelve compounds were identified, with Phenol, 2,6-dimethoxy- and Epicholestanol being the most prominent. ENFL exhibited significant antioxidant activity in both the DPPH scavenging assay (IC50: 19.6679 μg/mL) and the reducing power assay (RC50: 0.5925 mg/mL). The in-vivo anti-inflammatory assay showed the highest (42.51 % and 54.33 %) suppression of edema at the fourth hour at 200 and 400 mg/kg body weight of ENFL, respectively, while indomethacin exhibited 59.48 % inhibition. Moreover, all in-vivo analgesics tests demonstrated a significant dose dependent effect of ENFL at the experimental doses. In-silico studies screened Phenol, 2,6-dimethoxy- (CID-7041), as the most active compound, exhibiting stronger binding affinities to the cyclooxygenase-2 than other compounds. Additionally, ADME/T analysis indicated that the compound exhibited favorable pharmacokinetic properties and toxicity profiles. The current in-vitro, in-vivo, and in-silico investigations revealed analgesics and anti-inflammatory properties of Nypa fruticans leaves, supporting its potential as a natural drug for treating pain and inflammation.