Drinking water is as safe in South Bend as anywhere else in the country. Do not swim in the St. Joseph River or accidentally ingest river water as the Western half of the St. Joe is still quite polluted. A 5-phase project to reroute old stormwater pipelines out of the river is nearly halfway finished, and is the primary remaining obstacle toward relative purity.
Like many post-industrial cities, South Bend has some trouble spots. To be safe, lock your vehicle when you plan to leave it unattended anywhere downtown, but especially in a parking garage or low lit area after dark. Places to be careful during the day and not walk through after dark include areas on and around Lincoln Way West between William St. and the airport, SR 23 and Madison St. on the East Side of downtown and the river, Western Avenue between William St. and Mayflower, and US 31 between Monroe and Donmoyer Ave. to the north and south and Miami St. and Olive/Locust Rd. to the east and west. Essentially, the south and west sides of downtown and a small portion of the east side can be dangerous, but the majority of neighborhoods are safe. Portage Road and going north towards Cleveland is also known for crime. Take care as you would in any major city after dark.
One natural threat to be aware of are tornadoes: if you hear a siren or there is a tornado warning issued, take it seriously. Because South Bend/Michiana is so far North of the tornado belt, there are very few twisters in the area, even during tornado season. However, the tornadoes that do occur are usually F0s which, though comparatively weak, are often low to the ground and very difficult to spot with doppler radar, making advanced warning more difficult. Though much smaller events, their winds speeds can reach as high as 90 miles per hour and they can cause very localized damage in a short period.