Medicinal plants are rich in bioactive substances that may have therapeutic uses. Rhapis excelsa (Arecaceae), known for its anti-chikungunya and antioxidant properties, remains underexplored. The goal of this study was to examine the phytochemical profile, antioxidant activity, analgesic activity, and anti-inflammatory potential of the ethanolic extract of Rhapis excelsa leaves (EEREL). The antioxidant potential of EEREL was evaluated via TPC, TFC, TTC, H2O2 radical scavenging and TAC assays. In vivo studies demonstrated its anti-inflammatory and analgesic effects through the formalin-induced paw edema test and acetic acid-induced writhing test. GC–MS analysis revealed 32 major phytoconstituents, which were subsequently validated through molecular docking and molecular dynamics (MDS) simulations against the cyclooxygenase-2 (COX-2) enzyme. EEREL exhibited strong antioxidant potential, with high TFC (95.59 mg QE/g), TPC (261.38 mg GAE/g), TTC (743.96 mg GAE/g), TAC (338.18 mg AAE/g), and notable H2O2 scavenging activity (SC50 = 27.3 μg/mL). At doses of 200 and 400 mg/kg, it inhibited writhing by 57% and 72%, respectively, and reduced formalin-induced paw edema by 57.71% and 59.01%, respectively (∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001), demonstrating significant, dose-dependent antinociceptive and anti-inflammatory effects in mice. In an in-silico study, CID 160512, CID 7055, and CID 550196 were identified as the top docking-prioritized compounds against COX-2, with CID 160512 exhibiting the strongest binding affinity. Subsequent ADME/T, MDS, and MM-GBSA analyses further supported their favorable safety profiles, drug-likeness, and stability, suggesting that EEREL possesses promising analgesic and anti-inflammatory potential; however, further comprehensive investigations are warranted to confirm these findings.