A large volume of high-dimensional genetic data has been produced in modern medicine and biology fields. Data-driven decision-making is particularly crucial to clinical practice and relevant procedures. However, high-dimensional data in these fields increase the processing complexity and scale. Identifying representative genes and reducing the data’s dimensions is often challenging. The purpose of gene selection is to eliminate irrelevant or redundant features to reduce the computational cost and improve classification accuracy. The wrapper gene selection model is based on a feature set, which can reduce the number of features and improve classification accuracy. This paper proposes a wrapper gene selection method based on the slime mould algorithm (SMA) to solve this problem. SMA is a new algorithm with a lot of application space in the feature selection field. This paper improves the original SMA by combining the Cauchy mutation mechanism with the crossover mutation strategy based on differential evolution (DE). Then, the transfer function converts the continuous optimizer into a binary version to solve the gene selection problem.Firstly, the continuous version of the method, ISMA, is tested on 33 classical continuous optimization problems. Then, the effect of the discrete version, or BISMA, was thoroughly studied by comparing it with other gene selection methods on 14 gene expression datasets. Experimental results show that the continuous version of the algorithm achieves an optimal balance between local exploitation and global search capabilities, and the discrete version of the algorithm has the highest accuracy when selecting the least number of genes.