The drug-drug interactions (DDIs) are actions or events that occur when two or more drugs administered together, may cause a clinical significance or not. There are certain factors that may affect the severity of DDIs such as age, gender, number of drugs prescribed, and physician specialists. This study aims to answer: Is there DDI in Libyan community pharmacies? In addition, to explore the factors that might be affecting DDI. Drug Interactions Checkers are used. 200 prescriptions were collected randomly from two different areas ( high and low income),100 from each one and were used to investigate the DDIs by using two different sources (Drugs.com and BNF platforms), bearing in mind, age, gender, prescribers' specialty, and drug number (prescription size). A personal interview questionnaire with pharmacists for investigate a source of DDI knowledge was considered. The correlation test was used to analysis the findings. The randomly selected sample has 316 drug combinations. The study has revealed a minimum of three drugs (46.0%). In general, Drugs.com was the richer source of DDI than BNF (66.5% and 34.5%, respectively). It is found that 66.5% (67.0% of this is moderate DDI) of these combinations have DDI by Drugs.com. A significant correlation between DDI and gender (male > female, p = 0.035) was found. In a state of residential areas, the results are similar in both selected pharmacies. Most moderate DDIs (21.0% and 15.0%) are prescribed by orthopedics and psychiatrists, respectively. The observational interview questionnaire indicated that 100% of the participating pharmacists had no source of knowledge regarding DDI, 100% of 200 prescriptions had no chick it regarding DDI and 100% of found DDI is released to use by community pharmacies to patients. More than half of the prescribed drug combinations have DDIs (classified as moderate DDIs), and all of them are released for use by pharmacists.