"I leave this job with a sense of work unfulfilled because the world is a worse place now than when I joined in 2021," Griffiths said at his final news conference before he leaves at the end of June.
He said 300 million people worldwide need humanitarian aid and the amount required to assist has been determined to be $49 billion.
Griffiths said his office has only been able to gather $8 billion of the required amount.
"It's never been quite as difficult and as bad as it is now," he said.
Noting that some crises remained more prominent or a new crisis "superseded" another, he said when he started in 2021, the focus was on Ethiopia, then shifted to Afghanistan and with the start of the war in Ukraine, the attention turned there.
He said the situations in Sudan and the Gaza Strip subsequently became the main agenda items, while situations in Syria, Haiti and Yemen "still have great suffering."
Emphasizing that the Black Sea Grain Initiative signed with Türkiye's involvement was a very important humanitarian diplomacy victory, Griffiths said it showed that "enemies" could unite for the good of the world.
Sounding the alarm on Sudan, he said 5 million people are on the brink of famine.
Griffiths stated that the conflict could have been prevented but success was not achieved.
"We're not winning on ending conflict," he said. "The impunity that goes with the willingness of men to reach for the gun has also never been so great. The protection of civilians issue in the Security Council was a good resolution, but God knows it is a bad world.”
Highlighting the broader implications of the global humanitarian crisis, he said: "We are not resolving conflicts, we are not using dialogue where we had committed to use dialogue. The founders of the UN, the words of the UN Charter: ‘To save succeeding generations from the scourge of war’ -- we are failing them," he stressed.
Griffiths also pointed out that opportunities were not sufficiently utilized in Afghanistan and Yemen.
On Gaza, Griffiths said, "We won't leave but we're looking at aid operation which is not delivering.
"We're nowhere near where we need to be and indeed the levels of malnutrition among children have risen," he noted.
Describing the aid distribution as "unplannable," Griffiths noted that his office has been calling for a cease-fire for months.
He emphasized that priority should be given to humanitarian aid over the entry of private sector products. Griffiths said the people of Gaza do not have the money to buy the incoming products.
Griffiths said the increase in crime rates in Gaza was directly related to the lack of adequate aid, explaining that people had to attack trucks, which he did not condemn.
Regarding the US' floating dock, Griffiths said: "I was directly involved in trying to ensure that we had clarity of purpose."
He said that within this framework, an agreement was reached for the UN World Food Programme to handle the distribution, and after long negotiations, an agreement was also reached to address concerns about working in areas where Israeli forces would be present.
"UN will continue to be a central player in the provision of aid and indeed, in the mobilization of reconstruction assistance," said Griffiths, adding that the idea of deploying "UN peacekeepers in Gaza is delusional. It's not going to happen. We shouldn't rely on that."
Stressing that there needs to be a "much more aggressive approach to impunity," he said its continuation should not be allowed.
Noting that those who killed humanitarian aid workers in Gaza and bombed health facilities were not punished, Griffiths said it was also true in Ukraine and Sudan.