The rapid growth in biomedical datasets has generated high dimensionality features that negatively impact machine learning classifiers. In machine learning, feature selection (FS) is an essential process for selecting the most significant features and reducing redundant and irrelevant features. In this study, an equilibrium optimization algorithm (EOA) is used to minimize the selected features from high-dimensional medical datasets. EOA is a novel metaheuristic physics-based algorithm and newly proposed to deal with unimodal, multi-modal, and engineering problems. EOA is considered as one of the most powerful, fast, and best performing population-based optimization algorithms. However, EOA suffers from local optima and population diversity when dealing with high dimensionality features, such as in biomedical datasets. In order to overcome these limitations and adapt EOA to solve feature selection problems, a novel metaheuristic optimizer, the so-called improved equilibrium optimization algorithm (IEOA), is proposed. Two main improvements are included in the IEOA: The first improvement is applying elite opposite-based learning (EOBL) to improve population diversity. The second improvement is integrating three novel local search strategies to prevent it from becoming stuck in local optima. The local search strategies applied to enhance local search capabilities depend on three approaches: mutation search, mutation–neighborhood search, and a backup strategy. The IEOA has enhanced the population diversity, classification accuracy, and selected features, and increased the convergence speed rate. To evaluate the performance of IEOA, we conducted experiments on 21 biomedical benchmark datasets gathered from the UCI repository. Four standard metrics were used to test and evaluate IEOA’s performance: the number of selected features, classification accuracy, fitness value, and p-value statistical test. Moreover, the proposed IEOA was compared with the original EOA and other well-known optimization algorithms. Based on the experimental results, IEOA confirmed its better performance in comparison to the original EOA and the other optimization algorithms, for the majority of the used datasets.