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Quantitative systems pharmacology (QSP) models are often implemented using a wide variety of technical workflows and methodologies. To facilitate reproducibility, transparency, portability, and reuse for QSP models, we have developed gQSPSim, a graphical user interface–based MATLAB application that performs key steps in QSP model development and analyses. The capabilities of gQSPSim include (i) model calibration using global and local optimization methods, (ii) development of virtual subjects to explore variability and uncertainty in the represented biology, and (iii) simulations of virtual populations for different interventions. gQSPSim works with SimBiology‐built models using components such as species, doses, variants, and rules. All functionalities are equipped with an interactive visualization interface and the ability to generate presentation‐ready figures. In addition, standardized gQSPSim sessions can be shared and saved for future extension and reuse. In this work, we demonstrate gQSPSim’s capabilities with a standard target‐mediated drug disposition model and a published model of anti‐proprotein convertase subtilisin/kexin type 9 (PCSK9) treatment of hypercholesterolemia.