In substandard drugs enforcement, there is a need to develop reliable, fast, and inexpensive analytical methods. Due to its very characteristics, HPTLC offers opportunities for the development of methods that meet these requirements. This technique was used to develop and validate a method for the determination of sildenafil in pharmaceutical formulations from the licit and illicit supply chain in Burkina Faso. Taking into account optimization parameters such as measurement wavelength and mobile phase composition, the best elution quality is found at the maximum signals of spots on silica plates at 305 nm, using a mixture of dichloromethane-methanol mixture 9 : 1 (v/v) proportions. The method developed under these conditions was validated using the accuracy profile as a decision tool. The establishment of the response function curves allowed the choice of the polynomial function applied to the peak areas. This mathematical model provides a validity range between 0.4 and 0.6 mg/mL. The application of the developed and validated method to collected samples allowed the detection of two substandard drugs and confirmed the poor quality of drugs in the illicit market. More data using this approach in a variety of drug molecules could lead to the establishment of databases of counterfeit drugs in Burkina Faso.