Tetracarpidium conophorum nuts are nutrient-dense Nigerian snacks associated with weight regulation. This study explores the nuts' impact on adipose tissue gene expression associated with low-grade inflammation. Ethanol whole extract (EWE), ethyl-acetate fraction (EAF) and the resulting residue (RES) were orally administered once daily to MSG-induced obese rats for 6 weeks (n = 6). Afterward, the RNA synthesis of inflammation-associated genes was measured, and GC-MS ligands in the extract and fractions were docked against their protein products in silico. The study found that in obese animals, PPAR-γ and Adiponectin expressions were down-regulated, while TNF-α was up-regulated, indicating an increased low-grade inflammatory process in adipose tissue. After 6-week oral treatments with EWE, EAF and RES, PPAR-γ and Adiponectin expressions increased significantly, while TNF-α expression decreased, suggesting the modulation of obesity-induced inflammation in adipose tissue. The in silico molecular docking analysis identified four lead compounds likely responsible for the observed effect, namely 6-Isopropenyl-4,8a-dimethyl-4a,5,67,8,8a-hexahydro-1H-naphthalen-2-one, 9,12,15-Octadecatrienoic methyl ester (Z,Z,Z), 9,12,15-Octadecatrienoic acid and Hexanedioic acid, bis(2-ethylhexyl). Of these compounds, 6-Isopropenyl-4,8a-dimethyl-4a,5,67,8,8a-hexahydro-1H-naphthalen-2-one demonstrated the strongest affinity to the binding cavities of PPARγ (-7.3 kcal/mol), Leptin (-5.2 kcal/mol), Adiponectin (-7.1 kcal/mol) and TNF-α (-6.3 kcal/mol) and was better than the standard drug, Orlistat (-6.7, -4.4, -6.8 and - 4.5 kcal/mol, respectively). The study reveals that T. conophorum nuts possess bioactive compounds/drug candidates that can exert positive modulation, at the molecular level, the low-grade inflammatory process associated with obesity, which normally facilitates the outset of complications.