The use of natural plant-based remedies in traditional medicine has garnered attention for their potential benefits in treating various viral infections. Neem (Azadirachta indica), a tree native to the Indian subcontinent, has long been utilized in Ayurvedic and folk medicine for its wide range of therapeutic properties. This review explores the use of neem extract in the treatment of viral infections such as chickenpox (varicella) and smallpox (variola). Both of these diseases, caused by viruses from the herpes and poxvirus families, respectively, have historically imposed significant health burdens, particularly in regions with limited access to modern healthcare. With the advent of vaccines and antiviral drugs, their incidence has been dramatically reduced; however, neem remains a complementary remedy in many cultures. Neem soothing and antibacterial qualities make it effective in reducing itchiness and preventing infections when applied topically. Smallpox, a more severe and now eradicated disease caused by the variola virus, was once a major cause of morbidity and mortality. Historical accounts indicate that neem leaves were used in poultices and baths to relieve the fever and rash associated with smallpox outbreaks. Studies on neem antiviral capabilities suggest that its active compounds may inhibit viral replication by interfering with viral entry and protein synthesis. While modern scientific research on neem direct effects on the viruses causing chickenpox and smallpox is limited, in vitro and in vivo studies have shown neem extracts ability to suppress other viruses, such as dengue, HIV, and herpes simplex. This indicates a broad-spectrum antiviral potential that warrants further investigation. Additionally, neem immune-boosting properties may help the body mount a more effective response to viral infections by enhancing the production of white blood cells and stimulating macrophage activity.