Grouting is an effective method to reduce permeability and improve the mechanical performance of sand layers, preventing a disastrous inrush of sand and water. A scientific grouting design scheme is the premise for satisfying grouting reinforcement requirements. Due to a lack of theoretical basis for current grouting designs, grouting projects are conducted empirically and blindly. This paper presents a quantitative design method for grouting in sand layers. Based on this method, a quantitative design is realized for judgment of the grouting mode, determination of grouting range and calculation of grouting reinforcement effect. Moreover, for the fracture–compaction grouting mode, a theoretical model is proposed to calculate the grouting process, considering the coupling effect of grout flow and sand layer deformation. Meanwhile, a calculation method for reinforcement is put forward, which can connect macroscopic performance of the grouted body and individual performance of grout veins, compacted sand and undisturbed sand. In order to verify the efficiency of the grouting design method, it has been used in a sand grouting project in Qingdao Metro Line 2. In this project, judgment of the grouting mode, selection of grouting type and determination of grouting parameters have been completed based on the design method. Several inspection approaches have been performed to evaluate the effectiveness of the grouting design, showing that engineering stability was guaranteed after the grouting operation.