Background: Competency-based medical education involves continuous and multi-tiered assessment. Acquiring basic procedural skill competencies is essential to ensure patient safety. Simulation incorporates both training and feedback and provides opportunities to learners to practice skills and procedures in life-like settings. Aims and Objectives: The objective of this study was to assess the effectiveness in improving the knowledge, perception, and skill of the 2nd-year medical students after video- and mannequin-based demonstration for parenteral routes of drug administration. Materials and Methods: A cross-sectional and questionnaire-based study was conducted from November 2019 to January 2020 in the department of pharmacology. The technique of parenteral routes of drug administration was explained to the participants using two teaching methods – PowerPoint presentation with video demonstration and demonstration on mannequins. The knowledge of all the participants was assessed before demonstration. At the end of each teaching method, the knowledge, perception, and skill of all the participants were assessed. The responses of participants after each teaching method were compared and analyzed. Results: A total of 132 students participated in PowerPoint with video demonstration-based teaching and 115 students participated in mannequin-based teaching. Significant increase in the knowledge mean score was observed due to the introduction of both the methods of teaching when compared with pre-intervention score. However, gain in knowledge was better with video-based teaching than mannequin-based teaching. Mean perception and skill of the students was significantly higher in mannequin-based teaching. Conclusion: The study concludes that knowledge of medical undergraduates regarding parenteral drug administration was good with both the teaching methods, but confidence- and hassle-free administration skill, following all the steps can be achieved only by hands-on training like using mannequin.