This study was carried out to determine the “Effect of Metronidazole and Amoxicillin on Prevotella spp and Fusobacterium spp in Patients with Oral Infections Attending Central Hospital Warri. A total of 59 specimens were collected from patients with oral infection. The specimens were studied by culture, biochemical test using analytical profile index 20A kit, polymerase chain reaction test and antibiotic susceptibility test using the agar dilution method. Data was subjected to statistical analysis using ANOVA. Out of 59 specimens collected, 41 patients were infected while 18 patients were non-infected. The highest number of those infected were within the age of 31-40 years and the lowest number was within the age of 1-10 years and 61-70 years. Female patients within the age bracket of 21-40 years and male patients within 41-50 years were the most infected. The most predominant oral infection was caries with 12 (29.3%) and the highest number was seen in mayle with 22 (53.7%) while the lowest was seen in females with 19 (46.2%). Organisms isolated include Prevotella intermedia, Fusobacterium nucleatum, Porphyromonas gingivalis and Peptostreptococcus spp. The most occurring organism was Fusobacterium nucleatum with 15 (36.6%) while the least occurring was Porphyromonas gingivalis with 5 (12.2%). Co-infection of Fusobacterium nucleatum and Prevotella intermedia was seen in 1 (1.7%) patient with periodontitis. The PCR technique identified Fusobacterium nucleatum 4 (9.7%) and Porphyromonas gingivalis 2 (4.9%), the minimum inhibitory concentration of antibiotics on the anaerobes from oral infections. Peptostreptococcus spp was susceptible to metronidazole with the MIC of 0.25μg/ml and all resistant to amoxicillin. Prevotella intermedia was susceptible to amoxicillin with the MIC of 0.125μg/ml and all resistant to metronidazole. Porphyromonas gingivalis was sensitive to both metronidazole and amoxicillin with the MIC of 0.125μg/ml and 0.25μg/ml respectively. Fusobacterium nucleatum was susceptible to both metronidazole and amoxicillin with the MIC of 0.25μg/ml respectively. However, metronidazole was seen to be more effective than amoxicillin in the treatment of oral infection caused by anaerobes. In conclusion, the effectiveness of metronidazole and amoxicillin as the sole therapy in the treatment of oral infections caused by anaerobes may also be of importance in designing approaches to control periodontal infections.