Fracturing fluids are being increasingly used for viscosity development and proppant transport during hydraulic fracturing operations. Furthermore, the breaker is an important additive in fracturing fluid to extensively degrade the polymer mass after fracturing operations, thereby maximizing fracture conductivity and minimizing residual damaging materials. In this study, the efficacy of different enzyme breakers was examined in alkaline and medium-temperature reservoirs. The parameters considered were the effect of the breaker on shear resistance performance and sand-suspending performance of the fracturing fluid, its damage to the reservoir after gel breaking, and its gel-breaking efficiency. The experimental results verified that mannanase II is an enzyme breaker with excellent gel-breaking performance at medium temperatures and alkaline conditions. In addition, mannanase II did not adversely affect the shear resistance performance and sand-suspending performance of the fracturing fluid during hydraulic fracturing. For the same gel-breaking result, the concentration of mannanase II used was only one fifth of other enzyme breakers (e.g., mannanase I, galactosidase, and amylase). Moreover, the amount of residue and the particle size of the residues generated were also significantly lower than those of the ammonium persulfate breaker. Finally, we also examined the viscosity-reducing capability of mannanase II under a wide range of temperatures (104–158 °F) and pH values (7–8.5) to recommend its best-use concentrations under different fracturing conditions. The mannanase has potential for applications in low-permeability oilfield development and to maximize long-term productivity from unconventional oilwells.