The up-flow anaerobic sludge blanket (UASB) reactor for treating starch wastewater exhibits poor resistance to organic loading rate shocks and low efficiency in biomethane recovery. This study proposed a solution to address this issue by using oyster shells as an alternative conditioner. Results indicated that the UASB reactor with oyster shells conditioning exhibited a significant increase in methane production from 243 to 435 mL/g-chemical oxygen demand (COD)removed, as the organic loading rate increased from 2.5 to 7.1 kg-COD/(m3·d). This value surpassed that of the control reactor, which experienced a sharp decline in performance. Furthermore, it also exceeded the majority of reported methane yields ranging from 150 to 330 mL/g-CODremoved. The pH adjustment and additional supply of carbon dioxide from oyster shells was primarily responsible for the substantial increase in methane production. Moreover, oyster shell conditioning also resulted in improvements in specific methanogenic activity, extracellular polymeric substances protection, and settling capacity of anaerobic granular sludge, as well as the enrichment in Methanosaeta abundance, and strengthening of methanogenic functional activity. All these factors contributed to the successful methanogenesis of starch wastewater in UASB reactor through oyster shell conditioning. These findings highlighted the potential of using oyster shells as a favorable conditioner for optimizing UASB treatment of easily acidified wastewater (e.g., starch wastewater), which presented promising practical applications.