Background: Ficus semicordata Buch. is a well-known ethnomedicinal plant that is used to treat various ailments such as colic pain, urogenital difficulties, gastrointestinal disorders, visceral blockage, leprosy, jaundice, diabetes, and hepatitis. This study aims to investigate the phytochemical contents of the metabolites extracted (methanol) from the fruits of Ficus (F.) semicordata, and determine their neuropharmacological, anti-diarrhoeal, and cytotoxic potencies, using in vivo, in vitro, and in silico methods. Methods: The pharmacological properties of methanol extract of Ficus semicordata fruits (MEFSF) were assessed at different concentrations and its toxicity was determined using the in vitro brine shrimp lethality test. Tail suspension and forced swimming tests were used to investigate the antidepressant activity of MEFSF in mice and elevated plus maze and hole board test models were used to uncover its anxiolytic potentiality. The in vivo anti-diarrhoeal properties of MEFSF were tested on castor oil-induced diarrhoea and gastrointestinal motility models. Gas chromatography-mass spectrometry (GC-MS) analysis was conducted using a mass spectrometer. Based on the GC-MS analysis, 19 phytochemicals were investigated using molecular docking techniques against various target proteins to determine whether they mediate cytotoxic, depressive, anxiolytic, and anti-diarrhoeal effects. Results: MEFSF exhibited moderate toxicity (median lethal dose (LD₅₀): 267.23 μg/mL). In the antidepressant assessment, MEFSF demonstrated a significant (p < 0.0001) dose-dependent decrease in immobility compared to fluoxetine. Similarly, MEFSF exhibited a dose-dependent reduction in anxiolytic-like behaviour in mice, with a 400 mg/kg dose exhibiting vigorous activity. MEFSF also significantly inhibited motility in both anti-diarrhoeal models, with a 400 mg/kg dose exhibiting highly significant (p < 0.0001) suppression. The GC-MS analysis revealed 81 bioactive components. Seven phytochemicals exhibited a strong affinity for various target proteins in the molecular investigation. Notably, beta-D-glucopyranose and 4-O-beta-D-galactopyranosyl manifested a high affinity for hER, K⁺ channel, SERT3, and M3MAR and exhibited cytotoxic, anxiolytic, antidepressant, and anti-diarrhoeal potential. Conclusion: The findings indicate that MEFSF can potentially contribute to the development of innovative anti-cancer, neuropharmacological, and anti-diarrhoeal treatments. However, additional research is necessary to explore this possibility.