Membrane fouling and mineral scaling remain major drawbacks for MBR technology. Membrane fouling reduces the filtration ability in MBR systems by increasing transmembrane pressure (TMP) and thus increases the operational cost. This study focused on the application of commercially available antiscalant in a pilot MBR system and the effect of diffuser perforation diameter for the treatment of high mineral scaling propensity wastewater. Submerged flat sheet membranes (Kubota, nominal pore size: 0.4 µm) were used in the pilot-scale test unit operated in the wastewater treatment plant of ITOB Organized Industrial Zone, Izmir, Turkey. The commercially available antiscalants employed were coded AS-1 and AS-2 for antiscalant study. Long term effect of the two antiscalants employed was investigated under high mixed liquor suspended solid (MLSS) concentration (17–21 g/L) for two months of MBR operation. The effect of low MLSS concentration (10–13 g/L) was also studied without changing the concentration of antiscalant type and concentration. AS-1 was found to be more effective in terms of mineral scale control. The effect of diffuser perforation diameter (1, 3 and 5 mm) on mineral scaling minimization in MBR pilot system was also studied. The best performance with respect to membrane fouling control was found with an air diffuser having 3 mm of diffuser perforated diameter. Some quality analyses of the product water were also carried out to assess the effect of antiscalant addition on microbial activities in the MBR unit. The findings in this study reveal that the use of antiscalants has not affected biological treatment performance of MBR pilot system. The removal ranges obtained during all MBR studies were 98.47–99.9%, 84.62–99.4%, 89.5–98.5%, 86.90–99.9%, 67.01–99.2%, 75.03–93.9%, and 20.36–71.5% for total suspended solid (TSS), color, chemical oxygen demand (COD), NH4-N, PO4-P, NO2-N, and total nitrogen (TN) respectively.