The concurrent detection of gabapentin (GAP) and diclofenac K (DIC) in pharmaceutical formulations and wastewater has been made more approachable by developing and validating a precise Eco-friendly HPLC method. We evaluated the environmental impact of the RP-HPLC method using AGREEprep. This ensured that the technique was effective and sustainable Separation by HPLC was accomplished on a C18, 5 µm Hypersil column (150 mm × 4.6 mm) with a mobile phase composed of monobasic phosphate buffer pH 6.2: Methanol in a ratio of 50:50 and pumped at 1.5 mL/min. UV was detected at a wavelength of 210 nm and 275 nm for GAP and DIC, respectively. Obtaining retention times (Rt) of 1.30 min and 9.58 min, respectively. Limits of quantitation and detection, as well as specificity, linearity, precision, accuracy, robustness, and stability, were all validated for this technique per ICH requirements. The method was specific, precise, accurate, and reproducible. The linearity study was established for GAP and DIC in the 3-50 µg/mL range. It was discovered that the limits of both detection and quantification were 0.93 µg/mL and 2.82 µg/mL for GAP, whereas the results were 1.25 µg/mL and 3.78 µg/mL for GAP and DIC, respectively. Good accuracy, recovery, and precision of drugs from their commercial pharmaceutical formulations (99.01, 100.35%) and wastewater samples (100.84, 100.52%) for GAP and DIC, respectively. This approach has been effectively used for the quantitative measurement of GAP and DIC in commercial tablets and wastewater, and it is robust for minor or deliberate adjustments to the chromatographic variables.