Radiomics provides a structured approach to support clinical decision-making through key steps; however, users often face difficulties when switching between various software platforms to complete the workflow. To streamline this process, matRadiomics integrates the entire radiomics workflow within a single platform. This study extends matRadiomics to preclinical settings and validates it through a case study focused on early malformation differentiation in a zebrafish model. The proposed plugin incorporates Pyradiomics and streamlines feature extraction, selection, and classification using machine learning models (linear discriminant analysis—LDA; k-nearest neighbors—KNNs; and support vector machines—SVMs) with k-fold cross-validation for model validation. Classifier performances are evaluated using area under the ROC curve (AUC) and accuracy. The case study indicated the criticality of the long time required to extract features from preclinical images, generally of higher resolution than clinical images. To address this, a feature analysis was conducted to optimize settings, reducing extraction time while maintaining similarity to the original features. As a result, SVM exhibited the best performance for early malformation differentiation in zebrafish (AUC = 0.723; accuracy of 0.72). This case study underscores the plugin’s versatility and effectiveness in early biological outcome prediction, emphasizing its applicability across biomedical research fields.