Thin-layer chromatography (TLC) is an effective and simple technique for screening, evaluating, and quantifying low-quality and counterfeit pharmaceutical products. Smartphones have recently been used as accessible, cheap, and portable detectors that can replace more complicated analytical detectors. In this work, we have developed a simple and sensitive TLC method utilizing a smartphone charged-coupled device (CCD) camera not only to verify and quantify some gastrointestinal tract drugs, namely, loperamide hydrochloride (LOP) and bisacodyl (BIS), but also to detect acetaminophen (ACT) as a counterfeit drug. Both drugs (LOP and BIS) were chromatographed separately on a silica gel 60 F254 plate as a stationary phase under previously reported chromatographic conditions, using ethyl acetate:methanol:ammonium hydroxide (24:3:1, by volume) and ethyl acetate:methanol:glacial acetic acid (85:10:5, by volume) as developing systems to determine LOP and BIS, respectively. Universal stains, namely, iodine vapors and vanillin, were used to visualize the spots on the TLC plates to get a visual image using the smartphone camera and a spotlight as an illumination source with no need for a UV illumination source. The spot intensity was calculated using a commercially available smartphone application for quantitative analysis of the studied drugs utilizing ″acetaminophen″ as an example of a counterfeit substance. Rf values were calculated using the recorded images and found to be 0.77, 0.79, and 0.74 for LOP, BIS, and ACT, respectively, providing drug identity. Linear calibration curves using the smartphone–TLC method were obtained between the luminance and the corresponding concentrations over the ranges of 2.00–10.00 μg/mL and 1.00–10.00 μg/mL with limits of detection of 0.57 and 0.10 μg/mL for LOP and BIS, respectively. The suggested method was validated according to the International Conference of Harmonization (ICH) guidelines. The method was then successfully applied for the qualitative and quantitative determination of LOP or BIS as an example for gastrointestinal tract drugs in pure form and in their pharmaceutical dosage formulations. The proposed method is considered as a perfect alternative to traditional reported densitometric methods due to its simplicity, easy application, and inexpensiveness. No previously reported methods utilizing smartphones have been published for the determination of the studied drugs. The developed approach is considered the first TLC method using smartphones for the determination of some gastrointestinal tract drugs in their pure form and in pharmaceutical formulations.