Proteins are one of the primary building blocks that have significant functional properties to be applied in food and pharmaceutical industries. Proteins could be beneficial in their concentrated products or isolates, of which membrane-based filtration methods such as ultrafiltration (UF) encompass application in broad spectra of protein sources. More importantly, selective enrichment by UF is of immense interest due to the presence of antinutrients that may dominate their perspicuous bioactivities. UF process is primarily obstructed by concentration polarization and fouling; in turn, a trade-off between productivity and selectivity emerges, especially when pure isolates are an ultimate goal. Several factors such as operating conditions and membrane equipment could leverage those pervasive contributions; therefore, UF protocols should be optimized for each unique protein mixture and mode of configuration. For instance, employing charged UF membranes or combining UF membranes with electrodialysis enables efficient separation of proteins with a similar molecular weight, which is hard to achieve by the conventional UF membrane. Meanwhile, some proposed strategies, such as utilizing ultrasonic waves, tuning operating conditions, and modifying membrane surfaces, can effectively mitigate fouling issues. A plethora of advancements in UF, from their membrane material modification to the arrangement of new configurations, contribute to the quest to actualize promising potentials of protein separation by UF, and they are reviewed in this paper.