Sugarcane (Saccharum officinarum L.) is a highly valuable agricultural crop, cultivated globally in tropical and subtropical regions, primarily for its sugar content. Out of the 110 countries that grow sugarcane, India and Brazil together account for half of the world’s total production. Being an annual crop, it is prone to many diseases. The major diseases that can affect the sugarcane are red rot, wilt, sett rot, grassy shoot and pokkah boeng. Among the diseases Colletotrichum falcatum, Fusarium sacchari, Ceratocystis paradoxa, Candidatus Phytoplasma and Fusarium fujikuroi pathogen leads to more yield loss. Traditional disease management strategies, such as chemical treatments, conventional methods and biological control, offer limited protection throughout the crop cycle and raise concerns regarding environmental impact and sustainability. In recent years, plant growth-promoting microorganisms (PGPMs) have emerged as a promising alternative, offering environmentally friendly solutions to enhance plant health and manage diseases. RNAi has been explored to manage various diseases caused by viruses, fungi, and bacteria. By silencing key pathogenicity genes in the causal organisms, sugarcane mosaic virus (SCMV), smut, and leaf scald. The integration of PGPMs with RNAi emerging biotechnological tools and transcriptomics presents a sustainable approach to disease control, potentially reducing the dependency on chemical pesticides and promoting eco-friendly agricultural practices.