<p>This study presents a novel instrumental thin-layer chromatography (TLC) method developed for the simultaneous quantification of gabapentin and nortriptyline hydrochloride. Utilizing pre-coated TLC silica gel 60G F₂₅₄ plates as the stationary phase, the optimized mobile phase comprised toluene, methanol, and glacial acetic acid in a precise 7:3:0.1 (<i>V/V</i>) ratio. This carefully selected solvent system effectively resolves the chemically diverse analytes: gabapentin, a cyclohexane amino acid derivative with moderate polarity, and nortriptyline hydrochloride, a tricyclic compound characterized by an extensive aromatic structure and ionic properties. Detection was achieved via a dual-wavelength strategy. Nortriptyline hydrochloride, owing to its strong ultraviolet (UV) absorption, was directly monitored at 243 nm. In contrast, gabapentin was rendered detectable through a post-derivatization process using an alcoholic ninhydrin reagent, which converts it into a colored complex subsequently measured at 491 nm. This derivatization step is critical, as it enhances the chromophoric properties of gabapentin, facilitating its accurate quantification. The developed instrumental TLC method was thoroughly validated in accordance with international guidelines, demonstrating robust linearity, precision, accuracy, sensitivity, and reproducibility across the relevant concentration ranges. The simultaneous analysis approach significantly minimizes sample handling and analytical time, thereby reducing potential errors and enhancing throughput. Overall, this method offers a precise, reliable, and efficient analytical platform for the concurrent determination of gabapentin and nortriptyline hydrochloride, proving its utility for rigorous quality control and routine pharmaceutical analysis.</p>