This study aimed to evaluate the antioxidant, analgesic,neuropharmacological, antihyperglycemic, anti-inflammatory, andantidiarrheal properties of the methanolic extract of Nephelium lappaceumL. seeds (MSNL). In vitro antioxidant was determined using the DPPH freeradical scavenging test. Analgesic, antihyperglycemic, antidiarrheal, andanti-inflammatory activities were evaluated using the acetic acid-inducedwrithing test, oral glucose tolerance test, castor oil-induced diarrhea, andcarrageenan-induced paw edema, respectively, using rodents.Neuropharmacological activity was investigated in mice using bothopen-field and hole-cross methods. MSNL demonstrated strong DPPHscavenging capacity (IC50 = 53.92 μg/mL) compared to standard ascorbicacid (IC50 = 41.10 μg/mL). In the acetic acid-induced writhing test, thehighest dose (600 mg/kg) showed 59.89% inhibition of abdominalconstrictions compared to indomethacin (81.97%). MSNL showed asignificant (P<0.05, P<0.01) diminution in the locomotion of rodents in bothopen field, and hole cross methods at the highest dose compared to the controlgroup. MSNL significantly reduced blood glucose levels in mice (P<0.01,P<0.05) in a dose-dependent manner. The highest dose 600 mg/kg of MSNLshowed a significant 53.46% reduction in diarrhea. MSNL 600 mg/kgdisplayed significant inhibition of inflammation at the 3rd hour (65.22%).The findings demonstrated that the extract has potential bioactivities and canbe considered as the benchmark for the isolation of pure bioactivecompounds from this plant to discover new drugs.