To avoid conflicts among trains at stations and provide passengers with a periodic train timetable to improve service level, this paper mainly focuses on the problem of multi-periodic train timetabling and routing by optimizing the routes of trains at stations and their entering time and leaving time on each chosen arrival–departure track at each visited station. Based on the constructed directed graph, including unidirectional and bidirectional tracks at stations and in sections, a mixed integer linear programming model with the goal of minimizing the total travel time of trains is formulated. Then, a strategy is introduced to reduce the number of constraints for improving the solved efficiency of the model. Finally, the performance, stability and practicability of the proposed method, as well as the impact of some main factors on the model are analyzed by numerous instances on both a constructed railway network and Guang-Zhu inter-city railway; they are solved using the commercial solver WebSphere ILOG CPLEX (International Business Machines Corporation, New York, NY, USA). Experimental results show that integrating multi-periodic train timetabling and routing can be conducive to improving the quality of a train timetable. Hence, good economic and social benefits for high-speed rail can be achieved, thus, further contributing to the sustained development of both high-speed railway systems and society.