The primary purpose of the present study was to develop and validate a high‐performance thin‐layer chromatography method for quantitatively determining an anti‐hypertensive agent, perindopril erbumine, and moxonidine hydrochloride in bulk and synthetic mixture. The densitometric procedure was performed on aluminum thin‐layer chromatography plates pre‐coated with silica gel 60F254, employing a combination of dichloromethane: toluene: methanol: ammonia (7:1:2:0.1 v/v/v/v) as the mobile phase. The thin‐layer chromatography scanner was operated in absorbance mode at a wavelength of 223 nm to evaluate densitograms. The linearity of the method was established in the range of 1000–5000 ng/band for perindopril erbumine and 40–200 ng/band for moxonidine hydrochloride; the correlation coefficient (r2) was 0.9993 and 0.9983, respectively. The values of a limit of detection (186.06 and 3.51 ng/band, respectively, for perindopril erbumine and moxonidine hydrochloride) and limit of quantification (620.23 and 11.73 ng/band, respectively, for perindopril erbumine and moxonidine hydrochloride) have demonstrated the sensitivity of the developed method. The reported process was precise in both intra‐day and inter‐day analysis; the percentage relative standard deviation of peak area was less than 2% and has an accuracy within 100 ± 2%. The developed method has the potential to quantify perindopril erbumine and moxonidine hydrochloride from its synthetic mixture without any interference from other components or in quality control laboratories. [ABSTRACT FROM AUTHOR]