Aiming at the problems of poor initial population quality, slow convergence, and long-running time of optical microscope algorithm ( OMA), a multiple-strategy improved OMA based on periodical variation and encircling mechanism, called MOMA, was proposed in this paper. Firstly, the good point set population initialization is introduced to obtain a uniform initial population. Secondly, the periodic mutation and encircling mechanism are successively used to improve the convergence speed. Finally, the MOMA’s running time is optimized by introducing the conversion factor and the corresponding threshold, while balancing the exploration and exploitation. Experimental and analytical comparisons are made with OMA and 7 other excellent optimizers on 21 benchmark functions. The results show that MOMA largely outperforms the original algorithm. Furthermore, by applying MOMA to the optimization experiments of the no-wait flow-shop scheduling problem ( NWFSP), MOMA can obtain the optimal completion time and the fastest convergence speed compared to modified particle swarm optimization ( PSO) using adaptive strategy, grey wolf optimizer ( GWO), golden jackal optimization ( GJO), and OMA.