Colorectal Cancer (CRC) is defined as colon and rectum cancer and is among the major causes of mortality in developed Countries. Tarantula cubensis alcoholic extract (TCAE) and Nerium oleander distillate (NOD) are reported to have anticancer and antioxidative activity. In this study, it was aimed to research the impact on cell proliferation markers of TCAE and NOD given simultaneously in experimental colon cancer. A total of 24 rats, 6 in each group, were used in the study. Cancer Control (CC): Azoxymethane was administered at the beginning of the experiment at a dose of 15 miligrams (mg)· kilograms-1 (kg), (Subcutaneous, SC) twice, with an interval of a week (wk), to induce cancer. CC+TCAE: the dosage of Azoxymethane administered was 15 mg·kg-1 (SC) twice a wk at the beginning of the experiment, while in the case of TCAE, it was 0.2 mL·kg-1 (SC) once a wk for 18 wk from the beginning of the experiment. Fifteen mg·kg-1 (SC) of Azoxymethane was administered twice at one-wk intervals at the beginning of the experiment to the CC+NOD group, and NO distillate (NOD) was given with water throughout the experiment. Afterwards, animals were euthanized under appropriate conditions, paraffin blocks formed from colon tissues, histochemical AgNOR (Silverstained nucleolar organizer regions), and immunohistochemical PCNA (proliferating cell nuclear antigen) stainings were performed. In the study, immunohistochemically, PCNA scores and AgNOR count per nucleus (AgNCI) were significantly decreased in C-TCAE and C-NOD groups (P<0.001). AgNOR Area index (AgNAI) (P<0.01), Core Area Index (CAI) (P<0.05), and AgNOR Area index/Core Area Index (AgNAI/CAI) (P<0.01) scores were significantly decreased in the C-TCAE group. As a result, it was concluded that both TCAE and NOD are effective as chemopreventive drugs and that TCAE presents a more pronounced antiproliferative effect than NOD.