The invention discloses a method for comprehensively optimizing urban and rural bus timetable compiling and vehicle scheduling in districts. The method comprises the following steps: building a double-layer planning model; establishing an upper-layer vehicle scheduling model by taking the minimum bus operation cost as a target based on an upper-layer planning hypothesis condition; establishing a lower-layer time table optimization model by taking the total travel transfer time and transfer failure penalty of passengers in a district as a target based on lower-layer planning hypothesis conditions; solving a lower-layer time table optimization model, and outputting the optimized feasible task class set as a satisfactory solution of the lower-layer time table optimization model; solving the upper layer vehicle scheduling model, and outputting all task chains for completing the feasible task class set and the corresponding required vehicle number; and generating an optimal solution of thedouble-layer planning model to complete the output of the optimal vehicle scheduling scheme and the corresponding urban and rural bus timetable. Not only can the operation plan of district line organization be visually reflected, but also the convenient transfer demand of passengers and the effective configuration of enterprise vehicle resources can be further met.