<p>In light of the necessity for sustainable solutions in the construction industry and to minimize the environmental impact of extracting natural aggregates, this study investigates alternative aggregates, recycled gravel (RG), and crystallized slag (CSG), in concrete production. The objective of the research was to identify optimal substitution rates of natural aggregate by evaluating the fresh and mechanical properties of concrete at replacement rates of 50% and 100%. To this end, an innovative Box-Behnken Design (BBD) in conjunction with Response Surface Methodology (RSM) was adopted to optimize the mix design and predict the compressive and splitting tensile strengths of concrete. The incorporation of alternative aggregates led to an increased demand for superplasticizers while decreasing the density of fresh concrete. At a substitution rate of 50%, crystallized slag significantly enhanced mechanical strengths, which can be attributed to improved adhesion at the paste-aggregate interface and potential pozzolanic activity. While 50% substitution of natural aggregate by recycled gravel improved compressive strength, it also reduced tensile and flexural strengths, a phenomenon primarily attributed to its porosity and fractured nature. The microstructural analysis confirmed the influence of residual mortar in recycled aggregates and the alveolar structure of crystallized slag on concrete properties. The RSM modeling exhibited an excellent fit to experimental data for compressive and splitting tensile strength prediction, with R² values greater than 0.98. This study demonstrates the potential of alternative aggregates for sustainable concrete while emphasizing the need to optimize substitution rates and consider their specific characteristics in mixture formulation.</p>