In this paper, a Compton camera capable of estimating depth of interaction (DOI) in the detector was designed and optimized using Geant4. The proposed DOI Compton camera consists of two pixelated CsI(Tl) scintillators coupled with digital silicon photomultipliers [Digital Photon Counter (DPC)-3200-22]. The parameters affecting the performance of a Compton camera were evaluated for optimization in terms of image sensitivity and image resolution with a measure of figure of merit. The considered parameters were: 1) type of the reflector surface; 2) thickness of the scintillator; and 3) the distance between the scatter and the absorber detectors. The simulation results showed that a ground white surface is better than a polished white one. The optimal thickness and the scatter-absorber distance were found to be 15 mm and 4 cm, respectively. With the optimized parameters, performance of the DOI Compton camera was estimated for a ¹³⁷ Cs source at 1 m using Geant4. The image resolutions were 6.06° full-width at half-maximum with the list-mode maximum likelihood expectation maximization algorithm. It took 20 s to take Compton images for the gamma ray sources of 0.1 μSv/h intensity with the DOI Compton camera. It was shown that there was a clear improvement by employing DOI estimation algorithm in combination with the use of thick scintillators for a Compton camera.