Silicon photomultipliers (SiPM) are pixelated single-photon detectors combining high sensitivity, good time resolution and high dynamic range. They are emerging in many fields, such as time-domain diffuse optics (TD-DO). This is a promising technique in neurology, oncology, and quality assessment of food, wood, and pharmaceuticals. SiPMs can have very large areas and can significantly increase the sensitivity of TD-DO in tissue investigation. However, such improvement is currently limited by the high detector noise and the worsening of SiPM single-photon time resolution due to the large parasitic capacitances. To overcome such limitation, in this paper, we present two single-photon detection modules, based on 6 × 6 mm2 and 10 × 10 mm2 SiPMs, housed in vacuum-sealed TO packages, cooled to −15 °C and −36 °C, respectively. They integrate front-end amplifiers and temperature controllers, being very useful instruments for TD-DO and other biological and physical applications. The signal extraction from the SiPM was improved. The noise is reduced by more than two orders of magnitude compared to the room temperature level. The full suitability of the proposed detectors for TD-DO measurements is outside the scope of this work, but preliminary tests were performed analyzing the shape and the stability of the Instrument Response Function. The proposed modules are thus fundamental building blocks to push the TD-DO towards deeper investigations inside the body.