Mental fatigue poses a significant challenge to healthcare professionals in hospital settings, impairing cognitive performance, emotional well-being, and job satisfaction. This systematic review evaluates the effectiveness of cognitive interventions, including mindfulness programs, online psychological interventions, and telehealth cognitive-behavioral therapy (CBT), in mitigating mental fatigue among healthcare workers. A comprehensive literature search across PubMed, b-on, Web of Science, and Scopus identified six studies published between 2016 and 2023. These studies reported that cognitive interventions significantly reduced burnout and stress levels, with up to a 30% decrease in emotional exhaustion and improved coping mechanisms. In addition, participants demonstrated enhanced emotional well-being, reflected in increased mindfulness and life satisfaction scores of as much as 25%. Mindfulness-based programs and telehealth CBT were particularly effective in fostering resilience and improving overall cognitive function. However, the review also highlighted the need for future research to explore the long-term effects of these interventions, their cost-effectiveness, and innovative methods to improve accessibility and scalability, such as digital platforms. Integrating cognitive interventions into routine healthcare practice can enhance staff well-being, improve patient outcomes, and contribute to a more supportive work environment.