Plicosepalus is an important genus of the Loranthaceae family, and it is a semiparasitic plant grown in Saudi Arabia, traditionally used as a cure for diabetes and cancer in human and for increasing lactation in cattle. A flavonoid quercetin (P1), (-)-catechin (P2), and a flavane gallate 2S,3R-3,3',4',5,7-pentahydroxyflavane-5-O-gallate (P3) were isolated from the methanol extract of the aerial parts of P. curviflorus (PCME). The PCME and the isolated compounds were subjected to pharmacological assays to estimate peroxisome proliferator-activated receptors PPARα and PPARγ agonistic, anti-inflammatory, cytotoxic, and antimicrobial activities. Results proved for the first time the dual PPAR activation effect of the PCME and catechin (P2), in addition to the promising anti-inflammatory activity of the flavonoid quercetin (P1). Interestingly, both PCME and isolated compounds showed potent antioxidant activities while no antimicrobial effect against certain microbial strains had been reported from the extract and the isolated compounds. Based on the pharmacological importance of these compounds, an HPTLC validated method was developed for the simultaneous estimation of these compounds in PCME. It was found to furnish a compact and sharp band of compounds P1, P2, and P3 at R f = 0.34, 0.47, and 0.65, respectively, using dichloromethane, methanol, and formic acid (90 : 9.5 : 0.5, (v/v/v)) as the mobile phase. Compounds P1, P2, and P3 were found to be 11.06, 10.9, 6.96 μg/mg, respectively, in PCME. The proposed HPTLC method offers a sensitive, precise, and specific analytical tool for the quantification of quercetin, catechin, and flavane gallates in P. curviflorus.