The synthesis of bioactive oxazoles is often inefficient, and the reported methods remain largely unexplored for complex derivatives. To circumvent this issue, we have utilized a metal-free, photomediated [3 + 2] cycloaddition reaction between diazo compounds and nitriles, leading to a step- and reagent-economical synthesis of bioactive oxazoles. These exciting developments guided us in the efficient synthesis of oxazole-based natural products like annuloline, alkaloids like pimprinethine, labradorin 2, and oxazole-containing pharmaceuticals such as oxaprozin. Utilizing this approach, we have also demonstrated efficient synthesis of deuterium-labeled and heterocyclic-based oxazoles.