In the previous report, we reported that Hypomontagnella monticulosa originating from the rhizome of Zingiber griffithii was known to produce a marine-derived natural product. An OSMAC-based approach was designed by modifying the nutritional composition of the growth medium to investigate any possible new metabolites produced by the strain. The culture filtrate and biomass were conditioned through the use of three basal media, namely, Czapek-dox, potato dextrose, and Wickerham broth medium. GC-MS and multivariate analysis was performed to distinguish the chemicals and determine their composition in the tested extracts. Antimicrobial activity was tested against selected human pathogenic microbes using the disk-diffusion method. The MeOH extract of both culture filtrate and biomass from different fermentation media revealed that the majority of identified compounds (n = 40) were found in Wickerham medium (n = 23), which is later termed as MeOH-Wi. The chemical composition of MeOH-Wi was fatty acids (21.74 %), followed by terpenoids (17.38 %), cyclosiloxane (13.04 %), aldehydes (13.04 %), alkenes (8.7 %), hydrocarbons (8.7 %), esters (8.7 %), alkaloids (4.35 %), and an unclassified compound, the 9,9-Dimethyl-3,7-diazabicyclo[3.3.1]nonane. The numerous chemical compounds in MeOH-Wi corresponded with its antimicrobial activities against Micrococcus luteus NBRC 13,867 (±11 mm), Candida maltosa NBRC 1977 (±9 mm), and Escherichia coli JM 109 (±5 mm) which were higher than the other tested extracts. Further purification using HPLC RP-C18 using NP-SiO2/n-Hex-EtOAc (10:2) to yield compound (1). Compound (1) was determined as an analog of briarian W-a diterpene mostly found in marine sponge, Briareum spp.-as a pure compound in the MeOH extract of H. monticulosa based on the 1D and 2D NMR analysis. The anticancer activity (IC50) of compound (1) was 0.077, 0.080, and 0.102 µg/mL against the growth of HCT-116, NBT-T2, and Panc-1, respectively. As far as we are aware, this is the first report on finding a briarian diterpene that originates from an endophytic fungus, especially by H. monticulosa.