<p dir="ltr">Probiotics have become increasingly important in improving the health and diversity of the microbiota in our digestive system. Spray drying offers an affordable and effective way to encapsulate probiotics before consumption, where they are simultaneously covered in a wall material and rapidly dried to form microcapsules. In this review, we provide a chemical perspective towards spray drying, investigating the various interactions involved throughout the spray drying process. Various wall materials are discussed, such as carbohydrates (including newer wall materials like mucilages and exopolysaccharides), lipids and their constituents, as well as proteins (encompassing animal and plant protein). Specifically, we studied the chemical interactions observed between the spray-dried wall materials and the bacterial surface, as well as the formed microcapsule’s behavior in environmental stressors and gastrointestinal conditions. In addition, the synergistic effects between different types of wall materials, as well as additional effects like the Maillard reaction, were examined.</p>