Abstract Background Polymer gel dosimetry has been used extensively in radiation therapy for its capability in depicting a three dimensional view of absorbed dose distribution. However, more studies are required to find less toxic and more efficient polymers for application in radiotherapy dosimetry. Aim The purpose of this work was to evaluate the N-isopropyl acrylamide (NIPAM) gel dosimetric characteristics and optimize the protocol for X-ray computed tomography (CT) imaging of gel dosimeters for radiation therapy application. Material and methods A polymer gel dosimeter based on NIPAM monomer was prepared and irradiated with 60Co photons. The CT number changes following irradiation were extracted from CT images obtained with different sets of imaging parameters. Results The results showed the dose sensitivity of Δ N CT (H) = 0.282 ± 0.018 (H Gy −1) for NIPAM gel dosimeter. The optimized set of imaging exposure parameters was 120 kV p and 200 mA with the 10 mm slice thickness. Results of the depth dose measurement with gel dosimeter showed a great discrepancy with the actual depth dose data. Conclusion According to the current study, NIPAM-based gel dosimetry with X-ray CT imaging needs more technical development and formulation refinement to be used for radiation therapy application.