Microalgae-bacteria-based systems are an emerging and promising approach for wastewater treatment plants (WWTP), having nutrient and antibiotic resistance removal comparable to conventional technologies. Still, antibiotic-resistance genes and bacteria (ARG and ARB) can proliferate in microalga-bacteria aggregates (MABA), a concern to control. Different temperature regimes of MABA continuous anaerobic digestion (AD), thermophilic (55 °C), and mesophilic (35 °C) were evaluated in this study as a strategy to eliminate ARB and ARGs. Plate counting techniques and metagenomic-based analysis revealed that thermophilic temperature had a better performance, achieving ARB log reductions of 1.1 to 1.7 for various antibiotics and significantly reduced ARG concentrations up to 19.5 ± 0.8 ppm. The microbiome selection, the mobilome restriction, and directed functionality to thermal stress resistance were the main mechanisms responsible for resistome reduction at thermophilic conditions. Thermophilic AD effectively manages antibiotic resistance in microalgae-bacteria aggregates, which has important implications for wastewater treatment and reduces environmental risks.