Given its increasing prevalence, aging is of great concern to researchers worldwide. Cellular senescence is a physiological or pathological cellular state caused by aging and a prominent risk factor for the interruption of the integrity and functionality of human biological barriers. Health barriers play an important role in maintaining microenvironmental homeostasis within the body. The senescence of barrier cells leads to barrier dysfunction and age-related diseases. Cellular senescence has been reported to be a key target for the prevention of age-related barrier diseases, including Alzheimer's disease, Parkinson's disease, age-related macular degeneration, diabetic retinopathy, and preeclampsia. Drugs such as metformin, dasatinib, quercetin, BCL-2 inhibitors, and rapamycin have been shown to intervene in cellular senescence and age-related diseases. In this review, we conclude that cellular senescence is involved in age-related biological barrier impairment. We further outline the cellular pathways and mechanisms underlying barrier impairment caused by cellular senescence and describe age-related barrier diseases associated with senescent cells. Finally, we summarize the currently used anti-senescence pharmacological interventions and discuss their therapeutic potential for preventing age-related barrier diseases.