The near-infrared (nIR) fluorescence of polymer-wrapped single-walled carbon nanotubes (SWCNTs) is very sensitive to the local chemical environment. It has been shown that certain small reducing molecules can increase the fluorescence of SWCNTs. However, so far the role of the polymer around the SWCNT as well as the mechanism is not understood. Here, we investigated how reducing and oxidizing small molecules affect the nIR fluorescence of polymer-wrapped SWCNTs. Our results show that the polymer plays an essential role. Reducing molecules such as ascorbic acid, epinephrine, and trolox increased the nIR fluorescence up to 250% but only if SWCNTs were suspended in negatively charged polymers such as DNA or poly(acrylic acid) (PAA). In comparison, phospholipid−poly(ethylene glycol) wrapped SWCNTs did not respond at all while positively charged polyallylamine-wrapped SWCNTs were quenched. Oxidized equivalents such as dehydroascorbic acid did not show a clear tendency to quench or increase fluorescence. Only riboflavin with an intermediate oxidation potential and light absorption in the visible range quenched all polymerwrapped SWCNTs. In general, polymer-wrapped SWCNTs that responded to reducing molecules (e.g., +141%, ascorbic acid) also responded to oxidizing molecules (e.g., −81%, riboflavin). Nevertheless, several reducing molecules showed only a small fluorescence increase (NADH, +21%) or even a decrease (glutathione, −14%), which highlights that the redox potential alone cannot explain fluorescence changes. Furthermore, we show that neither changes of absorption cross sections, scavenging of reactive oxygen species (ROS), nor free surface areas on SWCNTs explain the observed patterns. However, results are in agreement either with a redox reaction of the polymer or conformational changes of the polymer that change fluorescence decay routes. In summary, we show that the polymer around SWCNTs governs how redox-active molecules change nIR fluorescence (quantum yield) of SWCNTs. Molecules with a low redox potential (<−0.4 V) are more likely to increase SWCNT fluorescence, but a low redox-potential alone is not sufficient.