Herein, an ecofriendly, simple, accurate, and cost‐effective high‐performance thin‐layer chromatography‐densitometic method was developed and optimized for separation and estimation of the novel triple therapy combination of Tinidazole, Clarithromycin, and Lansoprazole for treatment of Helicobacter pylori infection. Successful chromatographic separation was established using high‐performance thin‐layer chromatography silica gel 60 F254 plates as stationary phase and a developing system consisted of ethanol‐acetone‐ammonia (10.0:4.0:0.1, by volume). Scanning of the bands was accomplished at 210 nm. The presented method has been fully validated and found to be suitable for application in routine quality control of the studied drugs in their dosage form with average percent recoveries of 99.97 ± 0.62, 100.89 ± 0.51, and 99.78 ± 0.56% for Clarithromycin, Tinidazole and Lansoprazole, respectively. The developed method was assessed with four greenness evaluation tools; National Environmental Method Index, Analytical Eco‐scale, Green Analytical Procedure Index, and Analytical GREEnness Metric tool. The suggested method was demonstrated to be more environmental friendly than the reported high‐performance liquid chromatography one in terms of the use of hazardous chemicals and solvents, energy consumption, and waste generation.