The growing demand for sustainable construction materials has led to increased interest in utilizing industrial waste in concrete production. In particular, the replacement of conventional fillers with recycled materials presents both environmental and technical advantages. This study investigates the partial replacement of limestone filler (LF), with two powdered materials, waste glass powder (WGP) and waste expanded perlite (WEP), in desert sand concrete (DSC). The Design of Experiments technique was employed to assess the influence of these substitutions on the fresh and hardened properties of DSC, including workability, compressive strength, thermal conductivity, water absorption, and microstructure. Results showed that combining LF and WGP improved workability by up to 15.27%, while WEP tended to reduce it. Thermal conductivity was significantly reduced by WEP, achieving up to 15.29% reduction at full replacement. Compressive strength increased by up to 56% at 90 days with WGP, while ternary blends (LF-WGP-WEP) improved strength by 11.9%-24.85% compared to the control mix. Full replacement of LF with WGP also reduced water absorption by approximately 35.52%. SEM and EDX analyses revealed that WGP enhanced the microstructure and promoted C-S-H formation, contributing to reduced porosity and improved performance. These findings highlight the sustainable potential of reusing industrial waste in DSC to achieve both environmental and technical benefits. The approach supports circular economy principles and presents a promising solution for eco-efficient construction in arid regions.