Any issue or challenge that a person or partners encounter during any phase of typical sexual activity—be it physical pleasure, desire, preference, arousal, or orgasm—is referred to as sexual dysfunction. There are various factors that can contribute to this, such as the level of cortisol in the bloodstream. Cortisol is a hormone that is produced by the adrenal glands, which are situated above the kidneys. The release of cortisol is triggered by stress, whether it is caused by physical or mental factors. Cortisol plays a crucial role in priming the body for action when faced with stressful situations. The effects of this can lead to an elevation in blood pressure, a rise in blood sugar levels, and a weakening of the immune system, resulting in inflammation. The typical plasma concentration of cortisol (free and bound) is 12 mg/100 ml, while the average secretion amount is 15 mg per 24 h. This hormone also regulates the sleep/wake cycle. It is released during times of stress to provide the body with an energy boost and enhance its ability to cope with emergency situations. There are different medications and types of therapy available to assist individuals in overcoming sexual dysfunction. While there is limited information regarding the connection between cortisol and sexual dysfunction, existing literature suggests that elevated cortisol levels, such as those caused by stress, can increase the risk of experiencing sexual dysfunction. One of the most prevalent issues is erectile dysfunction. This chapter explores the biology and pathology of cortisol in sexual dysfunctions, providing a deeper understanding of the subject.