This study focuses on formulating and assessing an in-situ gastro-retentive gel for precise delivery of verapamil hydrochloride to the stomach, aiming to extend its residence time and improve targeted delivery. Gels were synthesized in-situ using a cation-controlled gelation method, incorporating varied blends of pectin and HPMCK4M. Design Expert’s box behnken design was employed to assess responses such as buoyancy lag time, water uptake, and cumulative drug discharge. Results revealed that the developed gels exhibited a total float time exceeding 10 hours, with formulation T-2 showing the least floating lag time and a cumulative drug release of 99.40 ± 3.24% over 10 hours. This suggests effective prolongation of the gastric residence time, enabling controlled verapamil hydrochloride release. Additional evaluations, including appearance, pH, viscosity, in-vitro gel formation, drug content, density, and gel force, supported the robustness of the developed gels. Subsequent in-vitro dissolution and stability studies affirmed consistent active ingredient content, highlighting formulation stability over time. In conclusion, this study demonstrates that the in-situ gels effectively extend gastric residence time, facilitating controlled verapamil hydrochloride release, marking significant advancements in drug delivery systems and targeted drug delivery within the gastrointestinal tract.