Early diagnosis of autism is extremely beneficial for patients. Traditional diagnosis approaches have been unable to diagnose autism in a fast and accurate way; rather, there are multiple factors that can be related to identifying the autism disorder. The gene expression (GE) of individuals may be one of these factors, in addition to personal and behavioral characteristics (PBC). Machine learning (ML) based on PBC and GE data analytics emphasizes the need to develop accurate prediction models. The quality of prediction relies on the accuracy of the ML model. To improve the accuracy of prediction, optimized feature selection algorithms are applied to solve the high dimensionality problem of the datasets used. Comparing different optimized feature selection methods using bio-inspired algorithms over different types of data can allow for the most accurate model to be identified. Therefore, in this paper, we investigated enhancing the classification process of autism spectrum disorder using 16 proposed optimized ML models (GWO-NB, GWO-SVM, GWO-KNN, GWO-DT, FPA-NB, FPA-KNN, FPA-SVM, FPA-DT, BA-NB, BA-SVM, BA-KNN, BA-DT, ABC-NB, ABC-SVM, ABV-KNN, and ABC-DT). Four bio-inspired algorithms namely, Gray Wolf Optimization (GWO), Flower Pollination Algorithm (FPA), Bat Algorithms (BA), and Artificial Bee Colony (ABC), were employed for optimizing the wrapper feature selection method in order to select the most informative features and to increase the accuracy of the classification models. Five evaluation metrics were used to evaluate the performance of the proposed models: accuracy, F1 score, precision, recall, and area under the curve (AUC). The obtained results demonstrated that the proposed models achieved a good performance as expected, with accuracies of 99.66% and 99.34% obtained by the GWO-SVM model on the PBC and GE datasets, respectively.