With the increase in life expectancy and awareness, more otorhinolaryngologic surgeries are being performed in the elderly population. Otorhinolaryngologic surgeries like septoplasty, tympanoplasty, and dacryocystorhinostomy (DCR) surgeries are elective surgeries for improving the quality of life. However, post-operative medication can entail a risk to life or serious side effects in elderly patients. It is seen that before any surgery, the patients have undergone various tests and investigations to monitor the nephrotoxicity and hepatotoxicity primarily to gauge medication clearance and organ damage. However, the effects of various post-operative medications on the central nervous system and cardiovascular system are less well-discussed. Harmful effects of various drugs especially antibiotics given post-operatively in otorhinolaryngology on the central nervous and cardiovascular system are not frequently reported, and the underlying mechanisms may be unclear or conflicting. Older individuals have a greater chance of experiencing serious drug reactions due to physiologic changes affecting pharmacokinetic processes. Some frailty risk indices can be used to determine the cognitive and physiological conditions in geriatric patients so that the outcome of using antibiotics in the post-operative period on the neuropsychiatric and cardiovascular systems can be predicted. This review aims to summarise the research on the neurotoxic and cardiac effects of antibiotics used in otorhinolaryngology practice in the post-operative period in elderly patients, with a focus on signs of psychosis, delirium, cognitive impairment, syncope, cardiac arrest, angina-like symptoms, etc. This review also studies some frailty risk indices that can be used to predict the neuropsychiatric and cardiac side effects due to polypharmacy, especially antibiotics. Hence, post-operative risks can be predetermined and a protocol for further management can be established.