Background: Habb-E-Shifa, Hamdard Sualin, and Hamdard Joshanda traditional herbal medicines may promote host resistance against infection by bacteria, viruses, and fungi which are easily accessible at inexpensive with no complexity. These herbal medicines are used to cure sore throat, cough, fever, lung cancer, and asthma patients in developing South Asian countries. These traditional herbal medicines acted a crucial role in the prevention and control of coronavirus disease 2019 (COVID-19). Aims and Objectives: This research article aimed at conducting phytochemistry, antimicrobial activity, COVID-19 docking and some spectroscopic (Infrared, Ultraviolet, 13C-Nuclear Magnetic Resonance (13C-NMR), 1H-NMR, and Mass Spectra) characterizations of the polyherbal drugs were carried out. Additionally, In-vitro and In-silico analyses were performed to measure activity against COVID-19. High Performance - Liquid Chromatography (HPLC), Gas Chromatography - Mass Spectrometry (GC-MS), antimicrobial, and docking studies were carried out. The preliminary phytochemical assay and bioactive compounds were screened using HPLC and GC-MS. The study is an attempt to assess the promising effects of selected polyherbal indigenous drugs such as Habb-E-Shifa, Hamdard Sualin, and Hamdard Joshanda phytoconstituents against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Materials and Methods: The extract of the selected polyherbal formulations showed high-to-moderate preventive effects on the growth inhibition in the pathogenic bacterium, namely Streptococcus oralis, Staphylococcus aureus, Propionibacterium acnes, Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris, and three fungal Candida albicans, Aspergillus fumigatus,and Aspergillus niger. Further docking study evaluates the pharmacological activity of bioactive chemical compounds with SARS-CoV-2 NSP5 (PDB ID: 7nxh) and SARS-CoV-2 Omicron spike protein with human angiotensin-converting enzyme 2 (ACE-2) (PDB ID: 7wk6). Results: In this study, for the first time, we attempted to examine some spectroscopic characterization of selected herbals. The total phenol content (1.66, 1.55, and 1.13 mg/mL) and total flavonoid content (4.92, 0.49, and 0.50 mg/mL) were present in the extracted samples of Habb-E-Shifa (H), Hamdard Joshanda (J), and Hamdard Sualin (S). Studies on COVID-19 docking infer the affinity of the herb's chemical components toward COVID-19 protease and ACE-2 receptor by establishing excellent binding capacity in complex formation. The results confirmed that polyherbal drugs harbor biological activities and thereby highlight that these extracts can serve as a remedy for antimicrobial and COVID-19. Conclusions: The research article confirms the remarkable potential in exhibiting antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. These herbal medicines such as Habb-E-Shifa (H), Hamdard Joshanda (J), and Hamdard Sualin (S) showed a vital role against SARS-CoV-2 Omicron spike protein with human ACE2 (7wk6) and amino acids of SARS-CoV-2 NSP5 (7nxh). Our study provides obvious evidence supporting dietary therapy and herbal medicine as potentially effective against SARS-CoV-2. Based on present studies, these herbal products can be introduced as preventive and therapeutic agents fight against coronavirus.