Antimicrobials are essential for combating infectious diseases. However, an increase in resistance to them is a major cause of concern. The empirical use of drugs in managing COVID-19 and the associated secondary infections have further exacerbated the problem of antimicrobial resistance. Hence, the situation mandates exploring and developing efficient alternatives for the treatment of bacterial and fungal infections in patients suffering from COVID-19 or other viral infections. In this review, we have described the alternatives to conventional antimicrobials that have shown promising results and are at various stages of development. An acceleration of efforts to investigate their potential as therapeutics can provide more treatment options for clinical management of drug-resistant secondary bacterial and fungal infections in the current pandemic and similar potential outbreaks in the future. The alternatives include bacteriophages and their lytic enzymes, anti-fungal enzymes, antimicrobial peptides, nanoparticles and small molecule inhibitors among others. What is required at this stage is to critically examine the challenges in developing the listed compounds and biomolecules as therapeutics and to establish guidelines for their safe and effective application within a suitable time frame. In this review, we have attempted to highlight the importance of rational use of antimicrobials in patients suffering from COVID-19 and boost the deployment of alternative therapeutics.