The search for potential signs of Martian life has been planned and implemented by worldwide countries for decades. Due to the high expenditure on Mars exploration, more easily accessible Mars-like regions on Earth are invaluable targets for astrobiology research to understand the detection of potential Martian biosignatures. In order to detect potential life signals beyond Earth, questions on how to define life and biosignatures need to be carefully inspected. This review summarizes scientific instrumental techniques, our “eyes” and “hands”, that facilitate identifying and quantifying biosignatures on Mars. Scientific devices that can be applied in astrobiology include electromagnetic spectrum-based spectrometers, mass spectrometers, redox potential indicators, circular dichroism polarimeters, in situ nucleic acid sequencers, life isolation/cultivation systems, and imagers. These techniques should be first tested in Mars analog extreme environments on Earth to validate their practicality on Mars. To better understand the instrumental detectability of biosignatures on Mars through its evolutionary history, terrestrial Mars analogs are divided into four major categories according to their similarities to different geological ages of Mars (the Early-Middle Noachian Period, the Late Noachian-Early Hesperian Period, the Late Hesperian-Early Amazonian Period, and the Middle-Late Amazonian Period). Future missions are suggested to explore more on the early terrains in Mars’ Southern Hemisphere once the landing issue is solved engineeringly, since these explorations permit investigating a continuum of the habitability shift through Mars geological history. Moreover, practical applications of scientific instruments listed above are briefly reviewed based on the four categories of Mars analogs, and instruments applied for autonomous robotic rover tests in Mars analogs are further discussed. For engineering efficiency, a Mars rover ought to be equipped with as few assemblable instruments as possible. Therefore, once candidate landing regions on Mars are defined, the portable suites of instruments should be smartly devised on the basis of the geological, geochemical, geomorphological, and chronological characteristics of the landing regions. Laboratory-based experiments without engineering restrictions are further encouraging and appealing if Mars sample-return missions are successfully completed. To exclude false positive and false negative conclusions in life discovery, the combined use and replication studies of multiple analytical techniques must be performed to confirm the observational results.