Oral care is a crucial challenge of nursing care in orally intubated patients. Oropharyngeal colonization with microorganisms is probably the first step in the pathogenesis of most bacterial pulmonary infections. This study aimed to investigate the effect of different oral care solutions on the oral health status of critically ill patients. We conducted a quasi-experimental study involving a convenience sample of 60 adult orally intubated patients, distributed equally into three groups: 20 patients received 0.12% chlorhexidine gluconate (CHX) solution as an oral rinse; 20 patients received 0.1% hexetidine (HEX) solution as an oral rinse; and a control group of 20 patients received routine hospital oral care with 0.9% normal saline (NS) solution. Oropharyngeal and tracheal cultures were obtained from patients within 24–48 h of admission, before the administration of topical oral antimicrobial solutions and then repeated on day 4 and day 7 after the oral solutions. The study revealed that CHX has a more powerful effect than HEX and NS in improving the oral mucosa and decreasing colonization of both the oropharynx and trachea. On day 7, the improvements were statistically significant in the CHX group and the HEX group (P = 0.02 and P = 0.03, respectively), but not in the NS group. This research confirms the effect of CHX and HEX in lowering the risk of tracheal and oropharyngeal colonization, and recommends the use of a CHX solution as oral mouth care in critically ill patients.