Sulfur disproportionation (S 0 DP) poses a challenge to the robust application of sulfur autotrophic denitrification due to unpredictable sulfide production, which risks the safety of downstream ecosystems. This study explored the S 0 DP occurrence boundaries with nitrate loading and temperature effects. The boundary values increased with the increase in temperature, exhibiting below 0.15 and 0.53 kg-N/m 3 /d of nitrate loading at 20 and 30 °C, respectively. A pilot-scale sulfur-siderite packed bioreactor (150 m 3 /d treatment capacity) was optimally designed with multiple subunits to dynamically distribute the loading of sulfur-heterologous electron acceptors. Operating two active and one standby subunit achieved an effective denitrification rate of 0.31 kg-N/m 3 /d at 20 °C. For the standby subunit, involving oxygen by aeration effectively transformed the facultative S 0 DP functional community from S 0 DP metabolism to aerobic respiration, but with enormous sulfur consumption resulting in ongoing sulfate production of over 3000 mg/L. Meanwhile, acidification by the sulfur oxidation process could reduce the pH to as low as 2.5, which evaluated the Gibbs free energy (ΔG) of the S 0 DP reaction to +2.56 kJ, thermodynamically suppressing the S 0 DP occurrence. Therefore, a multisubunit design along with S 0 DP inhibition strategies of short-term aeration and long-term acidification is suggested for managing S 0 DP in various practical sulfur-packed bioreactors.