The members of the genus Tanacetum have a long history in traditional medicine to manage several diseases. Thus, the present study attempts to determine the chemical composition and to probe into the biological activities of Tanacetum poteriifolium Grierson, a poorly studied medicinal plant. The enzyme inhibitory and antioxidant properties of the ethyl acetate, methanol, and water extracts were assessed using standard in vitro assays. Biological data were further investigated by multivariate analysis tools. The water extract showed the highest concentration of phenolics (83.38 mg gallic acid equivalent (GAE)/g extract), and was a potent radical scavenger (238.12 and 282.54 mg Trolox equivalent (TE)/g extract, towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), respectively) and had potent reducing power (555.03 and 285.79 mg TE/g extract, towards cupric reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP), respectively). The ethyl acetate extract (41.07 mg ethylenediaminetetraacetic acid equivalent (EDTAE)/g extract), rich in flavonoids (43.55 mg rutin equivalent (RE)/g extract), was a potent metal chelator. Besides, the ethyl acetate extract exhibited strong inhibitory action on cholinesterases (3.47 and 3.46 mg galantamine equivalent (GALAE)/g extract) and α-glucosidase (23.67 mmol acarbose equivalent (ACAE)/g extract). Tyrosinase was actively inhibited in the presence of the methanol extract of T. poteriifolium (128.54 mg kojic acid equivalent (KAE)/g extract). Liquid chromatography-electrospray ionisation quadrupole time-of-flight mass spectrometry analysis revealed the presence of quinic acid and methylquercetin derivatives in T. poteriifolium ethyl acetate extract. Two unknown compounds having m/z values 289.17, 267.23, 235.13, 211.14, 185.12, 121.06 and 275.21, 211.15, 171.11, 121.11 were identified from the T. poteriifolium methanol extract. Principal component analysis was performed to obtain an overview of the influence of solvents on T. poteriifolium biological activities which were satisfactorily discriminated. This study provides valuable baseline data on the biological activity of T. poteriifolium towards important enzymes targeted in the management of global health problems, such as Alzheimer's disease, diabetes, and epidermal hyperpigmentation problems.