In this study, the crude ethanol Rhynchosia nulubilis cultivated with Ganoderma lucidum mycelium (RNGM) extract was solvent fractionated with organic solvents such as n-hexane, chloroform, ethyl acetate, and water. The anticancer activities, anti-inflammatory activity total polyphenols, total flavonoids, isoflavones, and β-glucan of the solvent fractions of RNGM were studied. The ethyl acetate fraction showed the highest 2,2-diphenyl-1-picrylhydrazyl scavenging activity of 76.60% at 800 μg/mL. The ethyl acetate fraction also showed higher antioxidant activity in 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and ferric reducing ability of plasma assays compared to the other fractions. In addition, this study confirmed that the ethyl acetate fraction strongly inhibited nitric oxide production. The ethyl acetate fraction had the highest amount of total polyphenol and total flavonoid (65.33 mg gallic acid equivalent/g and 18.50 mg quercetin equivalent/g, respectively). The ethyl acetate fraction (13.02%) showed the highest amount of total β-glucan, followed by the water (6.32%), chloroform (1.43%), and n-hexane fraction (0.85%). Therefore, it is suggested that the ethyl acetate fraction of Rhynchosia nulubilis cultivated with Ganoderma lucidum mycelium may be potential natural sources for nutritional and pharmaceutical applications.