Over the past few decades, the health benefits are under threat as many commonly used antibiotics have become less and less effective against certain illnesses not only because many of them produce toxic reactions but also due to the emergence of drug-resistant bacteria. The clinical use of a combination of antibiotic therapy for Pseudomonas aeruginosa infections is probably more effective than monotherapy. The present study aims to estimate the antibacterial and antibiofilm activity of Conocarpus erectus leaves extracts against multi-drug resistant P. aeruginosa isolated from different hospitals in Baghdad city. One hundred fifty different clinical specimens were collected from patients from September 2021 to January 2022. All samples were cultured on specific and differential media, only 83 isolates were able to grow on cetrimide agar and at 42˚C, and then the VITEK 2 compact system was dependent to complete the identification. The results showed that the high resistance of the isolates was to the two antibiotics Ceftriaxone and Amoxicillin-Clavulanic acid with a percentage of (92.7%) and (89.2%) respectively, followed by Trimethoprim with a resistance rate of (79.5%). Ten isolates with multi-drug resistance are selected to evaluate the antibacterial activity of plant extracts and the combination between Conocarpus erectus extract and antibiotics. Maceration and Soxhlet apparatus were used to prepare the methanolic and aqueous extracts. The results of the radical scavenging ability showed that the methanolic and aqueous extracts (96.44 and 94.13%) in 10 mg/ml respectively, were more than the artificial antioxidant (BHT) which was 93.11% and the approach with the vitamin C which was 97.20%. The results of the total phenolic content were observed at 51.58 and 65.60 mg/g in 5 mg/ml for the aqueous and methanolic extracts respectively. The antibacterial activity of C. erectus leaves extracts showed that the methanolic extract was more effective than the aqueous extract at a concentration of 100 mg/ml. The results of the minimal inhibitory concentration (MIC) of the methanolic extract against P. aeruginosa were between 8-32 mg\ml. While the MIC values of the aqueous extract were 128-256 mg\ml. The synergistic activity between C. erectus methanolic extract and antibiotics against multidrug-resistant P. aeruginosa was assessed using the checkerboard analysis technique. The methanolic extract showed a synergistic effect with Cefepime against six isolates (FICI: ≤0.5), and an additive effect against four isolates (FICI: (≥ 0.5–1.0). Furthermore, a synergistic effect with Ceftriaxone against seven isolates and additive interaction was found against three isolates.