Self-medication (SM) with over-the-counter (OTC) medications is a prevalent issue in Afghanistan, largely due to poverty, illiteracy, and limited access to healthcare facilities. To better understand the problem, a cross-sectional online survey was conducted using a convenience sampling method based on the availability and accessibility of participants from various parts of the city. Descriptive analysis was used to determine frequency and percentage, and the chi-square test was used to identify any associations. The study found that of the 391 respondents, 75.2% were male, and 69.6% worked in non-health fields. Participants cited cost, convenience, and perceived effectiveness as the main reasons for choosing OTC medications. The study also found that 65.2% of participants had good knowledge of OTC medications, with 96.2% correctly recognizing that OTC medications require a prescription, and 93.6% understanding that long-term use of OTC drugs can have side effects. Educational level and occupation were significantly associated with good knowledge, while only educational level was associated with a good attitude towards OTC medications (p < 0.001). Despite having good knowledge of OTC drugs, participants reported a poor attitude towards their use. Overall, the study highlights the need for greater education and awareness about the appropriate use of OTC medications in Kabul, Afghanistan.