Introduction Rosuvastatin calcium is a strong HMG-CoA reductase inhibitor used to treat high cholesterol while Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used to help people with type 2 diabetes. Both medicines are often given together to patients who have both problems, to control fat levels and blood sugar levels. It is very important to measure these drugs correctly when they are combined, for quality control, making medicines and regular testing. This study worked on making and checking a simple, exact and strong RP-HPLC method and UV spectrophotometric method to measure Rosuvastatin calcium and Sitagliptin at the same time. Objective The main aim of this study was to create a tested reverse-phase high-performance liquid chromatographic (RP-HPLC) method along with UV spectrophotometric testing to measure Sitagliptin and Rosuvastatin calcium in pure form and mixed samples. Method A C18 column was used with a mobile phase made of Acetonitrile and Phosphate buffer in the right mix. Chromatographic separation was done using a C18 column (250 mm × 4.6 mm, 5 µm particle size) with a mobile phase made of Acetonitrile:Buffer 0.1% OPA -85:15%v/v The flow rate was kept at 1 millilitre per minute . UV spectrophotometric testing was also done at the 267 nm for Sitagliptin and Rosuvastatin calcium 244 nm wavelength. The method was checked by ICH Q2 (R1) rules, including system suitability, linearity, specificity, precision, accuracy, LOD, LOQ and robustness. Results The methods made showed very good linearity for both drugs in the chosen amount ranges. The recovery was between 98–102%, with %RSD values less than 2%, showing the method is very precise. LOD = 9.35 µg/mL and LOQ = 28.35 µg/mL.This means LOD = 1.07 µg/mL and LOQ = 3.25 µg/mL by HPLC . This means Sitagliptin can be measured correctly at this amount The method was specific and there was no problem from other ingredients. Conclusion The tested RP-HPLC and UV methods are simple, sensitive and reliable. They are good for regular testing of Sitagliptin and Rosuvastatin calcium in medicine forms.