As the typical toxic and hazardous gases, volatile organic compounds (VOCs) and hydrogen sulfide (H2S) pose a threat to the environment and human health. The demand for real-time detection of VOCs and H2S gases is growing in many application to protect human health and air quality. Therefore, it is essential to develop advance sensing materials for the construction of effective and reliable gas sensors. Herein, bimetallic spinel ferrites with different metal ions (MFe2O4, M = Co, Ni, Cu and Zn) were designed by using metal-organic frameworks as templates. The evaluation of cation substitution on crystal structures (inverse/normal spinel structure) and electrical properties (n/p type and band gap) is systematically discussed. The results indicate that p-type NiFe2O4 and n-type CuFe2O4 nanocubes with inverse spinel structure exhibit high response and great selectivity towards acetone (C3H6O) and H2S, respectively. Moreover, the two sensors also display the detection limits as low as 1 ppm (C3H6O) and 0.5 ppm (H2S), which are far below the threshold values of 750 ppm to acetone and 10 ppm to H2S for 8 h exposure set by American Conference of Governmental Industrial Hygienists (ACGIH). The finding provides new possibilities for the design of high-performance chemical sensors, which display tremendous potential for practical applications.