Common cold and flu are frequently occurring in humans, if not managed, can cause secondary infections and other complications. It may be minimized by boosting immunity, which can be done by Unani Medicine. Objective of this study is to evaluate in vitro immunomodulatory and antimicrobial activity and safety of granules of Naque Nazla, a famous Unani infusion / decoction. Naque Nazla granules (NNG) were tested for its immunomodulatory activity by lymphocyte proliferation assay and macrophage phagocytosis and antimicrobial activity by well diffusion method. LC-MS and GC-MS was done for standardization. Acute toxicity study was carried as per OECD guidelines 423, to evaluate safety of granules. THP-1 cells study displayed EC50 value of 997.6 μg/mL with a proliferation of 53.95% at 1280 μg/mL. Phagocytosis assay displayed 67.85% phagocytosis at 1280 μg/mL, antimicrobial activity was tested against common respiratory tract bacteria which showed susceptibility against Klebsiella pneumoniae, Salmonella spp., Staphylococcus aureus, and Streptococcus pyogenes. LC-MS and GC-MS fingerprinting data was set in and revealed the presence of many phytochemicals. Acute toxicity study displayed the drug safe up to 2000 mg/kg. NNG displayed immunomodulatory and antimicrobial activity in in vitro study and was also found safe.