Over the past few years scientific research has opened up to the idea of using digital games for human-based studies. Fields such as Neuroscience, Medical and Affective Computing are currently using games to study human-based phenomena. Even though a vast amount of work exists within the field, rarely is the subject of designing such games ever touched upon. In fact a common problem within the field is that the games themselves are often an afterthought, where certain gameplay limitations are never truly acknowledged and tend to be mostly ignored. Thus, this paper intends to provide some game design guidelines to the most common problems found in literature from work specifically using games for human physiological data-collection purposes. Furthermore, a brief description of the most popular physiological recording methods: Skin Conductance (SC), Heart-Rate Variability (HRV), Electromyogram (EMG), Electroencephalogram (EEG) and Functional Magnetic Resonance Imaging (fMRI); are provided as the game-play “limitations” of using such devices are an important factor to take into consideration in the game design process. As such, the objective of this paper is to provide awareness of specific game design limitations found in literature and analyse them from a game design perspective.