The extension of green and sustainable materials in the preparation of heterogeneous catalysts for organic transformations has increased over the past few decades. Because of their unique and intriguing physical and chemical properties, two-dimensional (2D) nanostructured materials have attracted widespread attention and have been used in a variety of applications, such as catalysis, electronics, and energy storage. A promising pathway to enhance the performance of 2D nanomaterials is their coupling with other functional materials to form heterogeneous or hybrid structures. Herein, we discuss the use of 2D-based nanostructured catalysts for enhancing organic transformations and highlight selected examples to demonstrate the synthesis, advantages, challenges, efficiency, and reusability of the introduced heterogeneous catalysts for cross-coupling and reduction reactions.