Protein-Protein Interaction (PPI) is a network of protein interconnections which regulates most of the biological methods. A sound state of biota largely depends on synchronized interactions between protein molecules, and any aberrant interactions between protein molecules may lead to complications, including cervical leukemia, tuberculosis, and other neural disorders. In PPI investigation, a plethora of computational methods have been developed over the years to analyze and predict PPI conclusively; however, a majority of these techniques proved to be strenuous and expensive. Therefore, the need for faster, accurate, and critical analysis of PPI warrants the adoption of Machine Learning (ML) methods such as Support Vector Machine (SVM), Artificial Neural Network (ANN), and Random Forest Model (RFM). These classifiers are useful in PPI unfolding in terms of amino acid sequence data. The SVM classifier, in particular, is serviceable in solving a majority of complex classification problems producing robust results in a reasonable time frame. This publication summarizes some state-of-art SVM based PPI investigations and challenges incurred in the application of the SVM method.INDEX TERMS Artificial neural network, machine learning, protein-protein interaction, support vector machine.• Detection of protein complexes.• Identification of domain interactions.