Gastrointestinal tract drugs are one of the important tools used to improve some of the problems affecting the gastrointestinal tract. Among these problems; peptic ulcer disease, gastroesophageal reflux disease and persistent dyspepsia are the most common. Drugs chosen in this work are H2- receptor antagonists (ranitidine HCl and famotidine), proton pump inhibitors (PPI; omeprazole and pantoprazole sodium), tinidazole and doxycycline which used in combination with PPI as triple therapy for treatment of H. pylori. The present work suggests different spectrophotometric methods for the determination of ranitidine HCl, famotidine, omeprazole and pantoprazole sodium. These methods provide simple, sensitive and inexpensive analytical procedures for estimation of the cited drugs either in pure forms or in their pharmaceutical formulations without interference from common excipients. RP-HPLC method was also one of the objectives of this study. This method was concerned with separation and determination of mixture of omeprazole, tinidazole and doxycycline in the presence of degradation products of omeprazole and tinidazole. The plan of the work comprises application of the proposed methods on drug products, validation of the methods and statistical comparison with the reported or official methods.