In medicinal chemistry, privileged structures are frequently used as an effective template for finding new drugs. Chalcone is a typical simple sugar that occurs in a wide variety of naturally occurring compounds. Chalcone derivatives are also prepared in large quantities due to their simple synthesis. These organic substances and synthetic ones have demonstrated a wide range of intriguing biological behaviors with therapeutic potential for treating several diseases. This review aims to draw attention to recent research that shows chalcone to be a preferred solvent in medicinal chemistry. The primary goals of this review are to provide comprehensive information on chalcone-based hybrids, discuss recent advancements in the chemistry of chalcones with their diverse bioactive implications for the eradication of disease, and develop novel hybrids with desirable therapeutic mechanisms.