The successful completion of the Chang'e-5 lunar exploration mission marks the beginning of China's lunar sampling efforts. To obtain lunar surface geological information and address the unique environmental conditions of the Moon, such as low gravity and the absence of a circulating medium, helical drill tools demonstrate good performance in drilling and sampling. To achieve better sampling results and improve the drilling and sampling rate, this study combines two drilling parameters—rotational speed and drilling speed—and four drill tool structural parameters—drill tool length, inner diameter, pitch, and helix height—totaling six parameters. Using orthogonal experiments, simulated lunar soil drilling and sampling tests were conducted. At the same time, the range analysis and variance analysis were used to analyze the results of the two test indexes of sampling rate and density change rate, and the following conclusions were obtained: (1) the influence degree of each factor under the indexes of sampling rate and density change rate was obtained respectively. (2) The influence trends of each factor on sampling rate and density change rate were obtained. (3) The optimal combination of parameters under the two test indexes of sampling rate and density change rate was obtained.