Mesembrine-type alkaloids are reported to be responsible for the psychoactive properties of Sceletium tortuosum. The aim of the study was to develop a simple, rapid and precise HPTLC densitometric method for the simultaneous determination of mesembrenol, mesembranol, mesembrine and mesebrenone in S. tortuosum raw materials and commercial products. Silica gel 60 F254 pre-coated glass plates were used with a mobile phase of DCM, MeOH and 10% NH3 (90:10:0.1 v/v/v). Densitometric quantification was performed in absorbance mode at 280 nm and good separation was obtained using a single mobile phase. Regression analyses of the calibration data showed good linear relationships with regression coefficient (r2) values ranging from 0.994 to 0.999. The method was validated for linearity, accuracy, limit of detection (LOD), limit of quantification (LOQ) and precision (repeatability). The results showed good correlation with data obtained from GC/MS analysis (reference method). The method proved to be specific, with potential application for rapid quantitative analyses of pharmacologically active alkaloids in S. tortuosum raw materials and commercial products.