Seven-membered nitrogen-containing heterocycles, particularly azepine-based compounds, represent an intriguing class of molecules with vast arrays of applications. These compounds have garnered considerable attention in synthetic and medicinal chemistry due to their non-planar, non-aromatic features, which offer structural flexibility and diversity to design new drugs with improved pharmacological properties. This review summarizes the recent advances in the synthesis of azepine derivatives, including eco-friendly methodologies that align with the principles of green chemistry, which emphasize atom economy, sustainability, and waste reduction. Besides, the present article highlights diverse biological activities, viz. anticancer, antibacterial, antifungal, antiviral, anti-inflammatory, and neuroprotective effects of azepine derivatives. Additionally, the review discusses key aspects such as molecular docking studies, structure-activity relationships (SAR), and mode of action evident through preclinical and clinical trials. The information presented in the current review article would assist researchers in designing and developing novel azepine-based leads for varied therapeutic applications.